J. J. Smit, A. H. Schinkel, O. Elferink, R. P. Groen, A. K. Wagenaar et al., Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease, Cell, vol.75, pp.451-462, 1993.

S. Ruetz and P. Gros, Phosphatidylcholine translocase: a physiological role for the mdr2 gene, Cell, vol.77, pp.1071-1081, 1994.

E. Jacquemin, Role of multidrug resistance 3 deficiency in pediatric and adult liver disease: one gene for three diseases, Semin Liver Dis, vol.21, pp.551-562, 2001.

O. Rosmorduc, B. Hermelin, P. Y. Boelle, R. Parc, J. Taboury et al., ABCB4 gene mutation-associated cholelithiasis in adults, Gastroenterology, vol.125, pp.452-459, 2003.

D. Degiorgio, C. Colombo, M. Seia, L. Porcaro, L. Costantino et al., Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3), Eur J Hum Genet, vol.15, pp.1230-1238, 2007.

G. U. Denk, H. Bikker, L. Dit-deprez, R. H. Terpstra, V. Van-der-loos et al., ABCB4 deficiency: a family saga of early onset cholelithiasis, sclerosing cholangitis and cirrhosis and a novel mutation in the ABCB4 gene, Hepatol Res, vol.40, pp.937-941, 2010.

R. Poupon, V. Barbu, P. Chamouard, D. Wendum, O. Rosmorduc et al., Combined features of low phospholipid-associated cholelithiasis and progressive familial intrahepatic cholestasis 3, Liver Int, vol.30, pp.327-331, 2010.

I. Giovannoni, F. M. Santorelli, M. Candusso, D. Rocco, M. Bellacchio et al., 568 and Asian children with progressive familial intrahepatic cholestasis type 3, Dig Liver Dis, vol.43, pp.567-570, 2011.

T. Dzagania, G. Engelmann, D. Haussinger, L. Schmitt, C. Flechtenmacher et al., The histidine-loop is essential for transport activity of human MDR3. A novel mutation of MDR3 in a patient with progressive familial intrahepatic cholestasis type 3, Gene, vol.506, pp.141-145, 2012.

R. Poupon, O. Rosmorduc, P. Y. Boelle, Y. Chretien, C. Corpechot et al., Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients, HEPATOLOGY, vol.58, pp.1105-1110, 2013.

I. Sabirzhanova, L. Pacheco, M. Rapino, D. Grover, R. Handa et al., Rescuing trafficking mutants of the ATP-binding cassette protein, ABCA4, with small molecule correctors as a treatment for stargardt eye disease, J Biol Chem, vol.290, pp.19743-19755, 2015.

J. Gautherot, A. M. Durand-schneider, D. Delautier, J. L. Delaunay, A. Rada et al., Effects of cellular, chemical, and pharmacological chaperones on the rescue of a trafficking-defective mutant of the ATP-binding cassette transporter proteins ABCB1/ABCB4, J Biol Chem, vol.287, pp.5070-5078, 2012.

J. L. Delaunay, A. M. Durand-schneider, C. Dossier, T. Falguieres, J. Gautherot et al., A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3, HEPATOLOGY, vol.63, pp.1620-1631, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01258764

R. Gordo-gilart, S. Andueza, L. Hierro, P. Jara, and L. Alvarez, Functional rescue of trafficking-impaired ABCB4 mutants by chemical chaperones, PLoS One, vol.11, p.150098, 2016.

J. K. Zolnerciks, E. J. Andress, M. Nicolaou, and K. J. Linton, Structure of ABC transporters, Essays Biochem, vol.50, pp.43-61, 2011.

A. Davit-spraul, E. Gonzales, C. Baussan, and E. Jacquemin, The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects, Semin Liver Dis, vol.30, pp.134-146, 2010.

J. F. Lucena, J. I. Herrero, J. Quiroga, B. Sangro, J. Garcia-foncillas et al., A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis, Gastroenterology, vol.124, pp.1037-1042, 2003.

A. Floreani, I. Carderi, D. Paternoster, G. Soardo, F. Azzaroli et al., Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy, Dig Liver Dis, vol.40, pp.366-370, 2008.

H. Yu, B. Burton, C. J. Huang, J. Worley, D. Cao et al., Ivacaftor potentiation of multiple CFTR channels with gating mutations, J Cyst Fibros, vol.11, pp.237-245, 2012.

F. Van-goor, S. Hadida, P. D. Grootenhuis, B. Burton, D. Cao et al., Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770, Proc Natl Acad Sci U S A, vol.106, pp.18825-18830, 2009.

F. J. Accurso, S. M. Rowe, J. P. Clancy, M. P. Boyle, J. M. Dunitz et al., Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation, N Engl J Med, vol.363, pp.1991-2003, 2010.

B. W. Ramsey, J. Davies, N. G. Mcelvaney, E. Tullis, S. C. Bell et al., A CFTR potentiator in patients with cystic fibrosis and the G551D mutation, N Engl J Med, vol.365, pp.1663-1672, 2011.

J. C. Davies, C. E. Wainwright, G. J. Canny, M. A. Chilvers, M. S. Howenstine et al., Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation, Am J Respir Crit Care Med, vol.187, pp.1219-1225, 2013.

J. Gautherot, D. Delautier, M. A. Maubert, T. Ait-slimane, G. Bolbach et al., Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations, HEPATOLOGY, vol.60, pp.610-621, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00978286

P. C. Smith, N. Karpowich, L. Millen, J. E. Moody, J. Rosen et al., ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer, Mol Cell, vol.10, pp.139-149, 2002.

I. Callebaut, R. Eudes, J. P. Mornon, and P. Lehn, Nucleotide-binding domains of human cystic fibrosis transmembrane conductance regulator: detailed sequence analysis and three-dimensional modeling of the heterodimer, Cell Mol Life Sci, vol.61, pp.230-242, 2004.
URL : https://hal.archives-ouvertes.fr/hal-00085903

M. A. Marti-renom, A. C. Stuart, A. Fiser, R. Sanchez, F. Melo et al., Comparative protein structure modeling of genes and genomes, Annu Rev Biophys Biomol Struct, vol.29, pp.291-325, 2000.

J. L. Delaunay, A. M. Durand-schneider, D. Delautier, A. Rada, J. Gautherot et al., A missense mutation in ABCB4 gene involved in progressive familial intrahepatic cholestasis type 3 leads to a folding defect that can be rescued by low temperature, HEPATOLOGY, vol.49, pp.1218-1227, 2009.

T. Cantz, A. T. Nies, M. Brom, A. F. Hofmann, and D. Keppler, MRP2, a human conjugate export pump, is present and transports fluo 3 into apical vacuoles of Hep G2 cells, Am J Physiol Gastrointest Liver Physiol, vol.278, pp.522-531, 2000.

K. Kotha and J. P. Clancy, Ivacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence, Ther Adv Respir Dis, vol.7, pp.288-296, 2013.

H. A. Lewis, S. G. Buchanan, S. K. Burley, K. Conners, M. Dickey et al., Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator, EMBO J, vol.23, pp.282-293, 2004.

Z. Xu, L. S. Pissarra, C. M. Farinha, J. Liu, Z. Cai et al., Revertant mutants modify, but do not rescue, the gating defect of the cystic fibrosis mutant G551D-CFTR, J Physiol, vol.592, pp.1931-1947, 2014.

X. Liu and D. C. Dawson, Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators protect G551D but not Del-taF508 CFTR from thermal instability, Biochemistry, vol.53, pp.5613-5618, 2014.

D. M. Cholon, N. L. Quinney, M. L. Fulcher, C. R. Esther, J. Das et al., Potentiator ivacaftor abrogates pharmacological correction of DeltaF508 CFTR in cystic fibrosis, Sci Transl Med, vol.6, pp.246-296, 2014.

K. Y. Jih and T. C. Hwang, Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle, Proc Natl Acad Sci U S A, vol.110, pp.4404-4409, 2013.

W. Y. Lin, K. Y. Jih, and T. C. Hwang, A single amino acid substitution in CFTR converts ATP to an inhibitory ligand, J Gen Physiol, vol.144, pp.311-320, 2014.

O. Moran, L. J. Galietta, and O. Zegarra-moran, Binding site of activators of the cystic fibrosis transmembrane conductance regulator in the nucleotide binding domains, Cell Mol Life Sci, vol.62, pp.446-460, 2005.

P. D. Eckford, C. Li, M. Ramjeesingh, and C. E. Bear, Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner, J Biol Chem, vol.287, pp.36639-36649, 2012.

J. P. Mornon, B. Hoffmann, S. Jonic, P. Lehn, and I. Callebaut, Fullopen and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics, Cell Mol Life Sci, vol.72, pp.1377-1403, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01134215

B. Delaunay and E. T. Al, HEPATOLOGY, vol.65, issue.2, 2017.

T. Ait-slimane, R. Galmes, G. Trugnan, and M. M. , Basolateral internalization of GPIanchored proteins occurs via a clathrin-independent flotillin-dependent pathway in polarized hepatic cells, Mol Biol Cell, vol.20, issue.17, pp.3792-800, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00579692

L. Aoudjehane, P. Y. Boelle, G. Bisch, R. Delelo, F. Paye et al., Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts, Lab Invest, vol.96, issue.6, pp.672-681, 2016.

P. Borst, N. Zelcer, and A. Van-helvoort, ABC transporters in lipid transport, Biochim Biophys Acta, vol.1486, issue.1, pp.128-172, 2000.

A. Bruneau, J. L. Delaunay, B. Hoffmann, A. M. Durand-schneider, V. Barbu et al., Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770), Hepatology, vol.65, issue.2, pp.560-70, 2017.

M. Cantore, R. Reinehr, A. Sommerfeld, M. Becker, and D. Haussinger, The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane, J Biol Chem, vol.286, issue.52, pp.45014-45043, 2011.

J. Chai, S. Y. Cai, X. Liu, W. Lian, S. Chen et al., Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis, J Hepatol, vol.63, issue.6, pp.1440-1448, 2015.

W. Chan, G. Calderon, A. L. Swift, J. Moseley, S. Li et al., Myosin II regulatory light chain is required for trafficking of bile salt export protein to the apical membrane in Madin-Darby canine kidney cells, J Biol Chem, vol.280, issue.25, pp.23741-23748, 2005.

J. L. Delaunay, A. M. Durand-schneider, D. Delautier, A. Rada, J. Gautherot et al., , pp.1218-1245

J. L. Delaunay, A. M. Durand-schneider, C. Dossier, T. Falguieres, J. Gautherot et al., A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3, Hepatology, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01258764

P. A. Gagliardi, L. Di-blasio, A. Puliafito, G. Seano, R. Sessa et al., PDK1-mediated activation of MRCKalpha regulates directional cell migration and lamellipodia retraction, J Cell Biol, vol.206, issue.3, pp.415-449, 2014.

J. Gautherot, D. Delautier, M. A. Maubert, T. Ait-slimane, G. Bolbach et al., Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations, Hepatology, vol.60, issue.2, pp.610-631, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00978286

V. Geenes and C. Williamson, Intrahepatic cholestasis of pregnancy, World J Gastroenterol, vol.15, issue.17, pp.2049-66, 2009.

H. Hayashi and Y. Sugiyama, Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances, Curr Mol Pharmacol, vol.6, issue.2, pp.95-103, 2013.

E. Jacquemin, D. Vree, J. M. Cresteil, D. Sokal, E. M. Sturm et al., The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood, Gastroenterology, vol.120, issue.6, pp.1448-58, 2001.

D. F. Ortiz, J. Moseley, G. Calderon, A. L. Swift, S. Li et al., Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells, J Biol Chem, vol.279, issue.31, pp.32761-70, 2004.

L. R. Pearce, D. Komander, and D. R. Alessi, The nuts and bolts of AGC protein kinases, Nat Rev Mol Cell Biol, vol.11, issue.1, pp.9-22, 2010.

F. A. Ran, P. D. Hsu, J. Wright, V. Agarwala, D. A. Scott et al., Genome engineering using the CRISPR-Cas9 system, Nat Protoc, vol.8, issue.11, pp.2281-308, 2013.

O. Rosmorduc, B. Hermelin, and R. Poupon, MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis, Gastroenterology, vol.120, issue.6, pp.1459-67, 2001.

S. Ruetz and P. Gros, Phosphatidylcholine translocase: a physiological role for the mdr2 gene, Cell, vol.77, issue.7, pp.1071-81, 1994.

C. M. Schonhoff, C. R. Webster, and M. S. Anwer, Taurolithocholate-induced MRP2 retrieval involves MARCKS phosphorylation by protein kinase C in HUH-NTCP Cells, Hepatology, vol.58, issue.1, pp.284-92, 2013.

I. Tan, J. Lai, J. Yong, S. F. Li, and T. Leung, Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase, FEBS Lett, vol.585, issue.9, pp.1260-1268, 2011.

I. Tan, K. T. Seow, L. Lim, and T. Leung, Intermolecular and intramolecular interactions regulate catalytic activity of myotonic dystrophy kinase-related Cdc42-binding kinase alpha, Mol Cell Biol, vol.21, issue.8, pp.2767-78, 2001.

M. Unbekandt and M. F. Olson, The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer, J Mol Med (Berl), vol.92, issue.3, pp.217-242, 2014.

Q. Venot, J. L. Delaunay, L. Fouassier, D. Delautier, T. Falguieres et al., A PDZ-Like Motif in the Biliary Transporter ABCB4 Interacts with the Scaffold Protein EBP50 and Regulates ABCB4 Cell Surface Expression, PLoS One, vol.11, issue.1, p.146962, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01274124

D. Q. Wang, D. E. Cohen, and M. C. Carey, Biliary lipids and cholesterol gallstone disease, J Lipid Res, vol.50, pp.406-417, 2009.

S. Wilkinson, H. F. Paterson, and C. J. Marshall, Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion, Nat Cell Biol, vol.7, issue.3, pp.255-61, 2005.

Z. Zhao and E. Manser, Myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK), the ROCK-like effectors of Cdc42 and Rac1, Small GTPases, vol.6, issue.2, pp.81-89, 2015.

J. K. Zolnerciks, E. J. Andress, M. Nicolaou, and K. J. Linton, Structure of ABC transporters, Essays Biochem, 2011.

J. L. Boyer, Bile formation and secretion, Compr Physiol, vol.3, pp.1035-1078, 2013.

T. Falguières, T. Aït-slimane, C. Housset, and M. Maurice, ABCB4: insights from pathobiology into therapy, Clin Res Hepatol Gastroenterol, vol.38, pp.557-563, 2014.

W. H. Admirand and D. M. Small, The physicochemical basis of cholesterol gallstone formation in man, J Clin Invest, vol.47, pp.1043-1052, 1968.

P. Borst, N. Zelcer, and A. Van-helvoort, ABC transporters in lipid transport, Biochim Biophys Acta, vol.1486, pp.128-144, 2000.

D. Q. Wang, D. E. Cohen, and M. C. Carey, Biliary lipids and cholesterol gallstone disease, J Lipid Res, vol.50, pp.406-411, 2009.

P. H. Dixon, Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking, Hum Mol Genet, vol.9, pp.1209-1217, 2000.

E. Jacquemin, The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood, Gastroenterology, vol.120, pp.1448-1458, 2001.

O. Rosmorduc, B. Hermelin, and R. Poupon, MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis, Gastroenterology, vol.120, pp.1459-1467, 2001.

J. L. Delaunay, A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3, Hepatology, vol.63, pp.1620-1631, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01258764

V. Vaut-hier, C. Houss-et, and T. Fa-lguieres, Targete d phar macot herapies for defe c t ive AB C t ransp or ters, Biochemical pharmacology, vol.136, pp.1-11, 2017.

R. Poupon, Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: An overview of their mechanisms of action, Clin Res Hepatol Gastroenterol, vol.36, issue.S3, p.12, 2012.

O. Rosmorduc and R. Poupon, Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene, Orphanet J Rare Dis, vol.2, p.29, 2007.

V. Geenes and C. Williamson, Intrahepatic cholestasis of pregnancy, World J Gastroenterol, vol.15, pp.2049-2066, 2009.

E. Jacquemin, Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis, Hepatology, vol.25, pp.519-523, 1997.

A. Davit-spraul, E. Gonzales, C. Baussan, and E. Jacquemin, Progressive familial intrahepatic cholestasis, Orphanet journal of rare diseases, vol.4, p.1, 2009.

J. L. Delaunay, Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770), Hepatology, vol.65, pp.560-570, 2017.

. Scientific-reports-|, , vol.9, p.6653, 2019.

J. Gautherot, Effects of Cellular, chemical and pharmacological chaperones on the rescue of a trafficking-defective mutant of the ATP-binding cassette transporters ABCB1/ABCB4, J Biol Chem, vol.287, pp.5070-5078, 2012.

E. J. Andress, A molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4, Hepatology, vol.59, pp.1921-1931, 2014.

H. J. Park, Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3, Sci Rep, vol.6, p.26872, 2016.

B. M. Foxwell, A. Mackie, V. Ling, and B. Ryffel, Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein, Mol Pharmacol, vol.36, pp.543-546, 1989.

I. Tamai and A. R. Safa, Competitive interaction of cyclosporins with the Vinca alkaloid-binding site of P-glycoprotein in multidrugresistant cells, J Biol Chem, vol.265, pp.16509-16513, 1990.

L. Meijer, Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5, European journal of biochemistry, vol.243, pp.527-536, 1997.

L. Meijer and E. Raymond, Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials, Accounts of chemical research, vol.36, pp.417-425, 2003.
URL : https://hal.archives-ouvertes.fr/hal-00020144

L. Meijer, Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis, Journal of innate immunity, vol.8, pp.330-349, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02042979

C. Norez, Roscovitine is a proteostasis regulator that corrects the trafficking defect of F508del-CFTR by a CDK-independent mechanism, British journal of pharmacology, vol.171, pp.4831-4849, 2014.

J. L. Delaunay, A missense mutation in ABCB4 gene involved in progressive familial intrahepatic cholestasis type 3 leads to a folding defect that can be rescued by low temperature, Hepatology, vol.49, pp.1218-1227, 2009.

R. Sormunen, S. Eskelinen, and V. P. Lehto, Bile canaliculus formation in cultured HEPG2 cells. Laboratory investigation; a journal of technical methods and pathology 68, pp.652-662, 1993.

L. Tang, Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives, J Biol Chem, vol.280, pp.31220-31229, 2005.

K. Bettayeb, Small-molecule inducers of Abeta-42 peptide production share a common mechanism of action, Faseb j, vol.26, pp.5115-5123, 2012.

D. Tougeron, G. Fotsing, V. Arbu, and M. B-e-auchant, AB CB4/MDR3 gene mutations and Cholangiocarcinomas, J Hepatol, vol.57, pp.467-468, 2012.

E. Jacquemin, Progressive familial intrahepatic cholestasis, Clin Res Hepatol Gastroenterol, vol.36, issue.1, pp.26-35, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01258764

A. Mehl, H. Bohorquez, M. S. Serrano, G. Galliano, and T. W. Reichman, Liver transplantation and the management of progressive familial intrahepatic cholestasis in children, World J Transplant, vol.6, pp.278-290, 2016.

D. Wessel, The natural course of FIC1 deficiency and BSEP deficiency: Initial results from the NAPPED-consortium (Natural course and Prognosis of PFIC and Effect of biliary Diversion, Journal of Hepatology, vol.68, pp.626-627, 2018.

S. Naoi, Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2, J Pediatr, vol.164, pp.1219-1227, 2014.

E. Gonzales, Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: Evidence for improvement of cholestasis with 4-phenylbutyrate, Hepatology, vol.62, pp.558-566, 2015.

R. Gordo-gilart, S. Andueza, L. Hierro, P. Jara, and L. Alvarez, Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones, PLoS One, vol.11, p.150098, 2016.

B. L. Shneider and J. Vockley, Possible Phenylacetate Hepatotoxicity During 4-Phenylbutyrate Therapy of Byler Disease, J Pediatr Gastroenterol Nutr, vol.62, pp.424-428, 2015.

L. Pena-quintana, M. Llarena, D. Reyes-suarez, and L. Aldamiz-echevarria, Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives, Patient preference and adherence, vol.11, pp.1489-1496, 2017.

W. F. De-azevedo, Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine, European journal of biochemistry, vol.243, pp.518-526, 1997.

S. Bach, Roscovitine targets, protein kinases and pyridoxal kinase, J Biol Chem, vol.280, pp.31208-31219, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00018751

M. C. Reichert and F. Lammert, ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum, Seminars in liver disease, vol.38, pp.299-307, 2018.

R. Poupon, Genotype-phenotype relationships in the low-phospholipid associated cholelithiasis syndrome. A study of 156 consecutive patients, Hepatology, vol.58, pp.1105-1110, 2013.

Y. Bacq, Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment, Dig Liver Dis, vol.49, pp.63-69, 2017.

U. Beuers, Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver, Hepatology, vol.33, pp.1206-1216, 2001.

F. Dombrowski, B. Stieger, and U. Beuers, Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver, Lab Invest, vol.86, pp.166-174, 2006.

S. Var-ma, Retargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis type 2, Hepatology, vol.62, pp.198-206, 2015.

J. Cicenas, Roscovitine in cancer and other diseases, Annals of translational medicine, vol.3, p.135, 2015.

E. J. Andress, M. Nicolaou, F. Mcgeoghan, and K. J. Linton, ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population, Cell Mol Life Sci, vol.74, pp.2513-2524, 2017.

J. Gautherot, Phosphorylation of ABCB4 impacts its function: Insights from disease-causing mutations, Hepatology, vol.60, pp.610-621, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00978286

U. K. Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature, vol.227, pp.680-685, 1970.

J. Van-meerloo, G. J. Kaspers, and J. Cloos, Cell sensitivity assays: the MTT assay, Methods Mol Biol, vol.731, p.13, 2011.

. Scientific-reports-|, , vol.9, p.6653, 2019.

S. Abu-hayyeh, G. Papacleovoulou, A. Lovgren-sandblom, M. Tahir, O. Oduwole et al., Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype, Hepatology, vol.57, issue.2, pp.716-742, 2013.

S. Abu-hayyeh and C. Williamson, Progesterone metabolites as farnesoid X receptor inhibitors, Dig Dis, vol.33, issue.3, pp.300-306, 2015.

F. J. Accurso, S. M. Rowe, J. P. Clancy, M. P. Boyle, J. M. Dunitz et al., Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation, N Engl J Med, vol.363, issue.21, pp.1991-2003, 2010.

W. H. Admirand and D. M. Small, The physicochemical basis of cholesterol gallstone formation in man, J Clin Invest, vol.47, issue.5, pp.1043-52, 1968.

K. Aida, H. Hayashi, K. Inamura, T. Mizuno, and Y. Sugiyama, Differential roles of ubiquitination in the degradation mechanism of cell surface-resident bile salt export pump and multidrug resistance-associated protein 2, Mol Pharmacol, vol.85, issue.3, pp.482-91, 2014.

L. Aleksandrov, A. Mengos, X. Chang, A. Aleksandrov, and J. R. Riordan, Differential interactions of nucleotides at the two nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator, J Biol Chem, vol.276, issue.16, pp.12918-12941, 2001.

L. A. Aleksandrov, J. F. Fay, and J. R. Riordan, R-Domain Phosphorylation by Protein Kinase A Stimulates Dissociation of Unhydrolyzed ATP from the First Nucleotide-Binding Site of the Cystic Fibrosis Transmembrane Conductance Regulator, Biochemistry, vol.57, issue.34, pp.5073-5078, 2018.

W. Almutawa, C. Smith, R. Sabouny, R. B. Smit, T. Zhao et al., The R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy, EBioMedicine, vol.45, pp.379-92, 2019.

G. Alpini, L. Baiocchi, S. Glaser, Y. Ueno, M. Marzioni et al., Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and secretion of BDL rats through activation of PKC alpha, Hepatology, vol.35, issue.5, pp.1041-52, 2002.

W. A. Alrefai and R. K. Gill, Bile acid transporters: structure, function, regulation and pathophysiological implications, Pharm Res, vol.24, issue.10, pp.1803-1826, 2007.

D. Alvaro, A. Cantafora, A. F. Attili, G. Corradini, S. et al., Relationships between bile salts hydrophilicity and phospholipid composition in bile of various animal species, Comp Biochem Physiol B, vol.83, issue.3, pp.551-555, 1986.

R. Ambadipudi and E. Georges, Sequences in Linker-1 domain of the multidrug resistance associated protein (MRP1 or ABCC1) bind to tubulin and their binding is modulated by phosphorylation, Biochem Biophys Res Commun, vol.482, issue.4, pp.1001-1007, 2017.

D. Amparan, A. D. Thomas, C. G. Lindahl, M. G. Yang, J. Bajaj et al., Direct interaction of myosin regulatory light chain with the NMDA receptor, J Neurochem, vol.92, issue.2, pp.349-61, 2005.

P. Angulo, Use of ursodeoxycholic acid in patients with liver disease, Curr Gastroenterol Rep, vol.4, issue.1, pp.37-44, 2002.

S. J. Aronson, R. S. Bakker, X. Shi, S. Duijst, T. Bloemendaal et al.,

A. Baghdasaryan, P. Chiba, and M. Trauner, Clinical application of transcriptional activators of bile salt transporters, Mol Aspects Med, vol.37, pp.57-76, 2014.

G. Bajaj, R. Rodriguez-proteau, A. Venkataraman, Y. Fan, C. Kioussi et al., MDR1 function is sensitive to the phosphorylation state of myosin regulatory light chain, Biochem Biophys Res Commun, vol.398, issue.1, pp.7-12, 2010.

G. Bajaj, Y. Zhang, M. I. Schimerlik, A. M. Hau, J. Yang et al., N-methyl-D-aspartate receptor subunits are non-myosin targets of myosin regulatory light chain, J Biol Chem, vol.284, issue.2, pp.1252-66, 2009.

A. Benedetti, M. Strazzabosco, O. C. Ng, and J. L. Boyer, Regulation of activity and apical targeting of the Cl-/HCO3-exchanger in rat hepatocytes, Proc Natl Acad Sci, vol.91, issue.2, pp.792-798, 1994.

N. Berkane, J. J. Cocheton, D. Brehier, P. Merviel, C. Wolf et al., Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy. A retrospective study of 19 cases, Acta Obstet Gynecol Scand, vol.79, issue.11, pp.941-947, 2000.

L. Bessonova, N. Volkova, M. Higgins, L. Bengtsson, S. Tian et al., Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor, Thorax, vol.73, issue.8, pp.731-771, 2018.

U. Beuers, M. Bilzer, A. Chittattu, G. A. Kullak-ublick, D. Keppler et al., Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver, Hepatology, vol.33, issue.5, pp.6509-6531, 2001.

K. M. Boberg and E. Schrumpf, Treatment of cholestatic liver diseases with ursodeoxycholic

, Tidsskr Nor Laegeforen, vol.117, issue.23, pp.3370-3373, 1997.

S. G. Bompadre, Y. Sohma, M. Li, and T. C. Hwang, G551D and G1349D, two CF-associated mutations in the signature sequences of CFTR, exhibit distinct gating defects, J Gen Physiol, vol.129, issue.4, pp.285-98, 2007.

P. Borst, A. Varadi, and K. Van-de-wetering, PXE, a Mysterious Inborn Error Clarified, Trends Biochem Sci, vol.44, issue.2, pp.125-165, 2019.

P. Borst, N. Zelcer, and A. Van-helvoort, ABC transporters in lipid transport, Biochim Biophys Acta, vol.1486, issue.1, pp.128-172, 2000.

R. Bossard, B. Stieger, B. O'neill, G. Fricker, and P. J. Meier, Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver, J Clin Invest, vol.91, issue.6, pp.2714-2734, 1993.

A. P. Bouin, A. Kyumurkov, M. Regent-kloeckner, A. S. Ribba, E. Faurobert et al., ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2-MRCKalpha balance, J Cell Sci, vol.130, issue.3, pp.626-662, 2017.

J. L. Boyer, Adaptative Regulation of Hepatocyte Transporters in Cholestasis, The Liver Biology and Pathobiology, 2009.

J. L. Boyer, Bile formation and secretion, Compr Physiol, vol.3, issue.3, pp.1035-78, 2013.

J. L. Boyer, M. Trauner, A. Mennone, C. J. Soroka, S. Y. Cai et al., Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents, Am J Physiol Gastrointest Liver Physiol, vol.290, issue.6, pp.1124-1154, 2006.

G. D. Branum, B. A. Bowers, C. R. Watters, J. Haebig, G. Cucchiaro et al., Biliary response to glucagon in humans, Ann Surg, vol.213, issue.4, pp.335-375, 1991.

A. Bretscher, D. Reczek, and M. Berryman, Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures, J Cell Sci, vol.110, pp.3011-3019, 1997.

J. M. Brown and L. Yu, Opposing Gatekeepers of Apical Sterol Transport: Niemann-Pick C1-Like 1 (NPC1L1) and ATP-Binding Cassette Transporters G5 and G8 (ABCG5/ABCG8), Immunol Endocr Metab Agents Med Chem, vol.9, issue.1, pp.18-29, 2009.

A. Bruneau, J. Delaunay, B. Hoffmann, A. M. Durand-schneider, V. Barbu et al., Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770), Hepatology, vol.65, issue.2, pp.560-70, 2017.

L. N. Bull, M. J. Van-eijk, L. Pawlikowska, J. A. Deyoung, J. A. Juijn et al., A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis, Nat Genet, vol.18, issue.3, pp.219-243, 1998.

M. G. Burbank, A. Burban, A. Sharanek, R. J. Weaver, C. Guguen-guillouzo et al., Early Alterations of Bile Canaliculi Dynamics and the Rho Kinase/Myosin Light Chain Kinase Pathway Are Characteristics of Drug-Induced Intrahepatic Cholestasis, Drug Metab Dispos, vol.44, issue.11, pp.1780-93, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01398437

E. Buschman, R. J. Arceci, J. M. Croop, C. M. Arias, I. M. Housman et al., mdr2 encodes P-glycoprotein expressed in the bile canalicular membrane as determined by isoform-specific antibodies, J Biol Chem, vol.267, issue.25, pp.18093-18102, 1992.

M. D. Buschman and S. J. Field, MYO18A: An unusual myosin, Adv Biol Regul, vol.67, pp.84-92, 2018.

Y. Calmus,

, Presse Med, vol.38, issue.9, pp.1307-1320, 2009.

A. F. Castro, J. K. Horton, C. G. Vanoye, and G. A. Altenberg, Mechanism of inhibition of Pglycoprotein-mediated drug transport by protein kinase C blockers, Biochem Pharmacol, vol.58, issue.11, pp.1723-1756, 1999.

N. M. Cerqueira, E. F. Oliveira, D. S. Gesto, D. Santos-martins, C. Moreira et al., Cholesterol Biosynthesis: A Mechanistic Overview, Biochemistry, vol.55, issue.39, pp.5483-506, 2016.

T. C. Chambers, J. Pohl, D. B. Glass, and J. F. Kuo, Phosphorylation by protein kinase C and cyclic AMP-dependent protein kinase of synthetic peptides derived from the linker region of human P-glycoprotein, Biochem J, vol.299, pp.309-324, 1994.

T. C. Chambers, J. Pohl, R. L. Raynor, and J. F. Kuo, Identification of specific sites in human Pglycoprotein phosphorylated by protein kinase C, J Biol Chem, vol.268, issue.7, pp.4592-4597, 1993.

I. Chandrasekar, Z. M. Goeckeler, S. G. Turney, P. Wang, R. B. Wysolmerski et al., Nonmuscle myosin II is a critical regulator of clathrin-mediated endocytosis, Traffic, vol.15, issue.4, pp.418-450, 2014.

X. B. Chang, A. Mengos, Y. X. Hou, L. Cui, T. J. Jensen et al., Role of N-linked oligosaccharides in the biosynthetic processing of the cystic fibrosis membrane conductance regulator, J Cell Sci, vol.121, pp.2814-2837, 2008.

X. Q. Chen, I. Tan, T. Leung, and L. Lim, The myotonic dystrophy kinase-related Cdc42-binding kinase is involved in the regulation of neurite outgrowth in PC12 cells, J Biol Chem, vol.274, issue.28, pp.19901-19906, 1999.

Z. Chen, T. Shi, L. Zhang, P. Zhu, M. Deng et al., Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade, Cancer Lett, vol.370, issue.1, pp.153-64, 2016.

X. Chi, S. Wang, Y. Huang, M. Stamnes, and J. L. Chen, Roles of rho GTPases in intracellular transport and cellular transformation, Int J Mol Sci, vol.14, issue.4, pp.7089-108, 2013.

J. Y. Chiang, Bile acids: regulation of synthesis, J Lipid Res, vol.50, issue.10, pp.1955-66, 2009.

J. E. Chin, R. Soffir, K. E. Noonan, K. Choi, and I. B. Roninson, Structure and expression of the human MDR (P-glycoprotein) gene family, Mol Cell Biol, vol.9, issue.9, pp.3808-3828, 1989.

S. Chin, M. Hung, A. Won, Y. S. Wu, S. Ahmadi et al., Lipophilicity of the Cystic Fibrosis Drug, Ivacaftor (VX-770), and Its Destabilizing Effect on the Major CF-causing Mutation: F508del, Mol Pharmacol, vol.94, issue.2, pp.917-942, 2018.

H. J. Cho, H. Y. Gee, K. H. Baek, S. K. Ko, J. M. Park et al., A small molecule that binds to an ATPase domain of Hsc70 promotes membrane trafficking of mutant cystic fibrosis transmembrane conductance regulator, J Am Chem Soc, vol.133, issue.50, pp.20267-76, 2011.

S. H. Choi, G. Czifra, N. Kedei, N. E. Lewin, J. Lazar et al., Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta, J Biol Chem, vol.283, issue.16, pp.10543-10552, 2008.

D. M. Cholon, N. L. Quinney, M. L. Fulcher, C. R. Esther, J. Das et al.,

, Potentiator ivacaftor abrogates pharmacological correction of DeltaF508 CFTR in cystic fibrosis, Sci Transl Med, vol.6, issue.246, pp.246-96, 2014.

J. P. Clancy, Z. Bebok, F. Ruiz, C. King, J. Jones et al., Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis, Am J Respir Crit Care Med, vol.163, issue.7, pp.1683-92, 2001.

J. P. Clancy, S. M. Rowe, Z. Bebok, M. L. Aitken, R. Gibson et al., No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations, Am J Respir Cell Mol Biol, vol.37, issue.1, pp.57-66, 2007.

R. Cmejla, J. Petrak, and J. Cmejlova, A novel iron responsive element in the 3'UTR of human MRCKalpha, Biochem Biophys Res Commun, vol.341, issue.1, pp.158-66, 2006.

R. Cmejla, P. Ptackova, J. Petrak, F. Savvulidi, J. Cerny et al., Human MRCKalpha is regulated by cellular iron levels and interferes with transferrin iron uptake, Biochem Biophys Res Commun, vol.395, issue.2, pp.163-170, 2010.

J. A. Cohn, T. V. Strong, M. R. Picciotto, A. C. Nairn, F. S. Collins et al., Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells, Gastroenterology, vol.105, issue.6, pp.1857-64, 1993.

L. K. Cole, J. E. Vance, and D. E. Vance, Phosphatidylcholine biosynthesis and lipoprotein metabolism, Biochim Biophys Acta, vol.1821, issue.5, pp.754-61, 2012.

C. Colombo, P. Vajro, D. Degiorgio, D. A. Coviello, L. Costantino et al., Clinical features and genotype-phenotype correlations in children with progressive familial intrahepatic cholestasis type 3 related to ABCB4 mutations, J Pediatr Gastroenterol Nutr, vol.52, issue.1, pp.73-83, 2011.

R. B. Cornell and N. D. Ridgway, CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis, Prog Lipid Res, vol.59, pp.147-71, 2015.

A. R. Crawford, A. J. Smith, V. C. Hatch, O. Elferink, R. P. Borst et al., Hepatic secretion of phospholipid vesicles in the mouse critically depends on mdr2 or MDR3 Pglycoprotein expression. Visualization by electron microscopy, J Clin Invest, vol.100, issue.10, pp.2562-2569, 1997.

L. Csanady, P. Vergani, and D. C. Gadsby, Structure, Gating, and Regulation of the Cftr Anion Channel, Physiol Rev, vol.99, issue.1, pp.707-745, 2019.

Y. J. Cui, X. Cheng, Y. M. Weaver, and C. D. Klaassen, Tissue distribution, gender-divergent expression, ontogeny, and chemical induction of multidrug resistance transporter genes (Mdr1a, Mdr1b, Mdr2) in mice, Drug Metab Dispos, vol.37, issue.1, pp.203-213, 2009.

L. C. Czuba, K. M. Hillgren, and P. W. Swaan, Post-translational modifications of transporters

, Pharmacol Ther, vol.192, pp.88-99, 2018.

E. Dassa, Natural history of ABC systems: not only transporters, Essays Biochem, vol.50, issue.1, pp.19-42, 2011.

J. C. Davies, S. Cunningham, W. T. Harris, A. Lapey, W. E. Regelmann et al., Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study, Lancet Respir Med, vol.4, issue.2, pp.107-122, 2016.

J. C. Davies, S. M. Moskowitz, C. Brown, A. Horsley, M. A. Mall et al., VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles, N Engl J Med, vol.379, issue.17, pp.1599-611, 2018.

J. C. Davies, C. E. Wainwright, G. J. Canny, M. A. Chilvers, M. S. Howenstine et al., J Respir Crit Care Med, vol.187, issue.11, pp.1219-1244, 2013.

A. Davit-spraul, E. Gonzales, C. Baussan, E. Jacquemin, A. Davit-spraul et al., The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects, Orphanet J Rare Dis, vol.4, issue.2, pp.134-180, 2009.

A. Davit-spraul, E. Gonzales, and E. Jacquemin, NR1H4 analysis in patients with progressive familial intrahepatic cholestasis, drug-induced cholestasis or intrahepatic cholestasis of pregnancy unrelated to ATP8B1, ABCB11 and ABCB4 mutations, Clinics and research in hepatology and gastroenterology, vol.36, issue.6, pp.569-73, 2012.

D. Boeck, K. Zolin, A. Cuppens, H. Olesen, H. V. Viviani et al., The relative frequency of CFTR mutation classes in European patients with cystic fibrosis, J Cyst Fibros, vol.13, issue.4, pp.403-412, 2014.

J. M. De-vree, E. Jacquemin, E. Sturm, D. Cresteil, P. J. Bosma et al., Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis, Proc Natl Acad Sci, vol.95, issue.1, pp.282-289, 1998.

M. Dean, The Human ATP-Binding Cassette (ABC) Transporter Superfamily2002

M. Dean and T. Annilo, Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates, Annu Rev Genomics Hum Genet, vol.6, pp.123-165, 2005.

R. G. Deeley, C. Westlake, and S. P. Cole, Transmembrane transport of endo-and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins, Physiol Rev, vol.86, issue.3, pp.849-99, 2006.

D. Degiorgio, A. Crosignani, C. Colombo, D. Bordo, M. Zuin et al., ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression, J Gastroenterol, vol.85, pp.1218-1245, 2015.

J. L. Delaunay, A. M. Durand-schneider, C. Dossier, T. Falguieres, J. Gautherot et al., A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3, Hepatology, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01258764

O. Demirel, I. Bangert, R. Tampe, and R. Abele, Tuning the cellular trafficking of the lysosomal peptide transporter TAPL by its N-terminal domain, Traffic, vol.11, issue.3, pp.383-93, 2010.

G. U. Denk, C. J. Soroka, Y. Takeyama, W. S. Chen, J. D. Schuetz et al., Multidrug resistanceassociated protein 4 is up-regulated in liver but down-regulated in kidney in obstructive cholestasis in the rat, J Hepatol, vol.40, issue.4, pp.585-91, 2004.

W. Dermauw and T. Van-leeuwen, The ABC gene family in arthropods: comparative genomics and role in insecticide transport and resistance, Insect Biochem Mol Biol, vol.45, pp.89-110, 2014.

D. Ciaula, A. Wang, D. Q. Bonfrate, L. Portincasa, and P. , Current views on genetics and epigenetics of cholesterol gallstone disease, Cholesterol, p.298421, 2013.

A. Dikkers and U. J. Tietge, Biliary cholesterol secretion: more than a simple ABC, World J Gastroenterol, vol.16, issue.47, pp.5936-5981, 2010.

V. Draheim, A. Reichel, W. Weitschies, and U. Moenning, N-glycosylation of ABC transporters is associated with functional activity in sandwich-cultured rat hepatocytes, Eur J Pharm Sci, vol.41, issue.2, pp.201-210, 2010.

M. Du, K. M. Keeling, L. Fan, X. Liu, T. Kovacs et al., Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model, J Mol Med (Berl), vol.84, issue.7, pp.573-82, 2006.

J. Eckstein, H. G. Holzhutter, and N. Berndt, The importance of membrane microdomains for bile salt-dependent biliary lipid secretion, J Cell Sci, vol.131, issue.5, 2018.

H. Einat, Partial effects of the protein kinase C inhibitor chelerythrine in a battery of tests for manic-like behavior in black Swiss mice, Pharmacol Rep, vol.66, issue.4, pp.722-727, 2014.

Y. Emi, S. Nomura, H. Yokota, and M. Sakaguchi, ATP-binding cassette transporter isoform C2 localizes to the apical plasma membrane via interactions with scaffolding protein, J Biochem, vol.149, issue.2, pp.177-89, 2011.

A. Esteller, Physiology of bile secretion, World J Gastroenterol, vol.14, issue.37, pp.5641-5650, 2008.

S. Etienne-manneville and A. Hall, Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta, Cell, vol.106, issue.4, pp.489-98, 2001.

T. Falguieres, T. Ait-slimane, C. Housset, and M. M. , ABCB4: Insights from pathobiology into therapy, Clinics and research in hepatology and gastroenterology, vol.38, issue.5, pp.557-63, 2014.

C. Ferrandiz-huertas, A. Fernandez-carvajal, and A. Ferrer-montiel, Rab4 interacts with the human P-glycoprotein and modulates its surface expression in multidrug resistant K562 cells, Int J Cancer, vol.128, issue.1, pp.192-205, 2011.

R. J. Ferreira, M. J. Ferreira, D. Santos, and D. J. , Assessing the Stabilization of P-Glycoprotein's Nucleotide-Binding Domains by the Linker, Using Molecular Dynamics. Mol Inform, vol.32, issue.5-6, pp.529-569, 2013.

R. Ferru-clement, F. Fresquet, C. Norez, T. Metaye, F. Becq et al., Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells, PLoS One, vol.10, issue.3, p.118943, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01141771

P. Fickert, A. Fuchsbichler, M. Wagner, G. Zollner, A. Kaser et al., Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice, Gastroenterology, vol.127, issue.1, pp.261-74, 2004.

R. Fiorotto, A. Villani, A. Kourtidis, R. Scirpo, M. Amenduni et al., The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity, Hepatology, vol.64, issue.6, pp.2118-2152, 2016.

S. Fiorucci, C. Clerici, E. Antonelli, S. Orlandi, B. Goodwin et al., Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis, J Pharmacol Exp Ther, vol.313, issue.2, pp.604-616, 2005.

C. Floquet, I. Hatin, J. P. Rousset, and L. Bidou, Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin, PLoS Genet, vol.8, issue.3, p.1002608, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00686519

R. C. Ford and K. Beis, Learning the ABCs one at a time: structure and mechanism of ABC transporters, Biochem Soc Trans, vol.47, issue.1, pp.23-36, 2019.

D. Fu, E. M. Van-dam, A. Brymora, I. G. Duggin, P. J. Robinson et al., The small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein, Biochim Biophys Acta, vol.1773, issue.7, pp.1062-72, 2007.

L. Fu, R. A. Tang, L. Bebok, Z. Rowe, S. M. Bartoszewski et al., DeltaF508 CFTR surface stability is regulated by DAB2 and CHIP-mediated ubiquitination in post-endocytic compartments, PLoS One, vol.10, issue.4, p.123131, 2015.

N. Ganne-carrie, C. Baussan, V. Grando, J. Gaudelus, D. Cresteil et al., Progressive familial intrahepatic cholestasis type 3 revealed by oral contraceptive pills, J Hepatol, vol.38, issue.5, pp.693-697, 2003.

M. L. Garcia-bermejo, F. C. Leskow, T. Fujii, Q. Wang, P. M. Blumberg et al.,

, Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha, J Biol Chem, vol.277, issue.1, pp.645-55, 2002.

S. Gasman, S. Chasserot-golaz, M. Malacombe, M. Way, and M. F. Bader,

, Mol Biol Cell, vol.15, issue.2, pp.520-551, 2004.

Z. C. Gatmaitan, A. T. Nies, and I. M. Arias, Regulation and translocation of ATP-dependent apical membrane proteins in rat liver, Am J Physiol, vol.272, issue.5, pp.1041-1050, 1997.

J. Gautherot, Maturation et trafic intracellulaire du transporteur biliaire ABCB4 : effet de mutations: Université Pierre et Marie Curie -Paris VI, 2012.

J. Gautherot, T. Claudel, F. Cuperus, C. D. Fuchs, T. Falguieres et al., Thyroid hormone receptor beta1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice, J Lipid Res, vol.59, issue.9, pp.1610-1619, 2018.

J. Gautherot, A. M. Durand-schneider, D. Delautier, J. L. Delaunay, A. Rada et al., Effects of cellular, chemical, and pharmacological chaperones on the rescue of a traffickingdefective mutant of the ATP-binding cassette transporter proteins ABCB1/ABCB4, J Biol Chem, vol.287, issue.7, pp.5070-5078, 2012.

T. Ge, X. Zhang, Y. Xiao, Y. Wang, and T. Zhang, Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease, BMC Med Genet, vol.20, issue.1, p.18, 2019.

A. Geier, M. Wagner, C. G. Dietrich, and M. Trauner, Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration, Biochim Biophys Acta, vol.1773, issue.3, pp.283-308, 2007.

F. T. Geillon, D. Gondcaille, C. Lizard, G. Savary, S. Transporteurs et al., Medecine/Sciences, vol.28, issue.12, 2012.

G. Gentric and C. Desdouets, Polyploidization in liver tissue, Am J Pathol, vol.184, issue.2, pp.322-353, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-01074730

U. A. Germann, T. C. Chambers, S. V. Ambudkar, T. Licht, C. O. Cardarelli et al., Characterization of phosphorylation-defective mutants of human P-glycoprotein expressed in mammalian cells, J Biol Chem, vol.271, issue.3, pp.1708-1724, 1996.

N. S. Ghonem, M. Ananthanarayanan, C. J. Soroka, and J. L. Boyer, Peroxisome proliferatoractivated receptor alpha activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion, Hepatology, vol.59, issue.3, pp.1030-1072, 2014.

F. Gibellini and T. K. Smith, The Kennedy pathway--De novo synthesis of phosphatidylethanolamine and phosphatidylcholine, IUBMB Life, vol.62, issue.6, pp.414-442, 2010.

A. Glantz, S. J. Reilly, L. Benthin, F. Lammert, L. A. Mattsson et al., Intrahepatic cholestasis of pregnancy: Amelioration of pruritus by UDCA is associated with decreased progesterone disulphates in urine, Hepatology, vol.47, issue.2, pp.544-51, 2008.

E. Golomb, X. Ma, S. S. Jana, Y. A. Preston, S. Kawamoto et al., Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family, J Biol Chem, vol.279, issue.4, pp.2800-2808, 2004.

E. R. Gomes, S. Jani, and G. G. Gundersen, Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells, Cell, vol.121, issue.3, pp.451-63, 2005.

N. Gomez-ospina, C. J. Potter, R. Xiao, K. Manickam, M. S. Kim et al., Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis, Nat Commun, vol.7, p.10713, 2016.

E. Gonzales, A. Davit-spraul, C. Baussan, C. Buffet, M. Maurice et al., Liver diseases related to MDR3 (ABCB4) gene deficiency, Front Biosci, vol.14, pp.4242-56, 2009.

E. Gonzales, B. Grosse, D. Cassio, A. Davit-spraul, M. Fabre et al.,

E. Gonzales, B. Grosse, B. Schuller, A. Davit-spraul, F. Conti et al., Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: Evidence for improvement of cholestasis with 4-phenylbutyrate, Hepatology, vol.62, issue.2, pp.558-66, 2015.

R. Gordo-gilart, S. Andueza, L. Hierro, P. Jara, and L. Alvarez, Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones, PLoS One, vol.11, issue.2, p.150098, 2016.

D. Gotthardt, H. Runz, V. Keitel, C. Fischer, C. Flechtenmacher et al., A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults, Hepatology, vol.48, issue.4, pp.1157-66, 2008.

P. Goubault, T. Brunel, A. Rode, B. Bancel, K. Mohkam et al., Low-Phospholipid Associated Cholelithiasis (LPAC) syndrome: A synthetic review, J Visc Surg, 2019.

M. E. Grassie, L. D. Moffat, M. P. Walsh, and J. A. Macdonald, The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1delta, Arch Biochem Biophys, vol.510, issue.2, pp.147-59, 2011.

J. W. Grisham, Organizational Principles of the Liver, The Liver Biology and Pathobiology, 52009.

A. Groen, M. R. Romero, C. Kunne, S. J. Hoosdally, P. H. Dixon et al., Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity, Gastroenterology, vol.141, issue.5, pp.1927-1964, 2011.

P. Gros, J. Croop, and D. Housman, Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins, Cell, vol.47, issue.3, pp.371-80, 1986.

H. M. Gu, G. Li, X. Gao, L. G. Berthiaume, and D. W. Zhang, Characterization of palmitoylation of ATP binding cassette transporter G1: effect on protein trafficking and function, Biochim Biophys Acta, vol.1831, issue.6, pp.1067-78, 2013.

S. Gupta, T. Stravitz, R. Pandak, W. M. Muller, M. et al., Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes, Hepatology, vol.32, issue.2, pp.341-348, 2000.

M. C. Hagemeijer, D. J. Siegwart, L. J. Strug, L. Cebotaru, M. J. Torres et al., Translational research to enable personalized treatment of cystic fibrosis, J Cyst Fibros, vol.17, issue.2S, pp.46-51, 2018.

L. R. Hagey, D. L. Crombie, E. Espinosa, M. C. Carey, H. Igimi et al., Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores, J Lipid Res, vol.34, issue.11, pp.1911-1918, 1993.

E. Halilbasic, T. Claudel, and M. Trauner, Bile acid transporters and regulatory nuclear receptors in the liver and beyond, J Hepatol, vol.58, issue.1, pp.155-68, 2013.

K. P. Harris and U. Tepass, Cdc42 and vesicle trafficking in polarized cells, Traffic, vol.11, issue.10, pp.1272-1281, 2010.

M. A. Hartman and J. A. Spudich, The myosin superfamily at a glance, J Cell Sci, vol.125, pp.1627-1659, 2012.

D. Haussinger, M. Schmitt, O. Weiergraber, and R. Kubitz, Short-term regulation of canalicular transport, Seminars in Liver Disease, vol.20, issue.3, pp.307-328, 2000.

H. Hayashi and Y. Sugiyama, 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps, Hepatology, vol.45, issue.6, pp.1506-1522, 2007.

Z. Hegyi and L. Homolya, Functional Cooperativity between ABCG4 and ABCG1 Isoforms, PLoS One, vol.11, issue.5, p.156516, 2016.

S. A. Henkel, J. H. Squires, M. Ayers, A. Ganoza, P. Mckiernan et al., Expanding etiology of progressive familial intrahepatic cholestasis, World J Hepatol, vol.11, issue.5, pp.450-63, 2019.

C. F. Higgins, ABC transporters: from microorganisms to man, Annual review of cell biology, vol.8, pp.67-113, 1992.

A. F. Hoffman, Bile Acids and the Enterohepatic Circulation, The Liver Biology and Pathobiology, vol.300, p.289, 2009.

L. Homolya, D. Fu, P. Sengupta, M. Jarnik, J. P. Gillet et al., LKB1/AMPK and PKA control ABCB11 trafficking and polarization in hepatocytes, PLoS One, vol.9, issue.3, p.91921, 2014.

A. Honda, T. Ikegami, M. Nakamuta, T. Miyazaki, J. Iwamoto et al., Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid, Hepatology, vol.57, issue.5, pp.1931-1972, 2013.

C. Housset, Y. Chretien, D. Debray, and N. Chignard, Functions of the Gallbladder, Compr Physiol, vol.6, issue.3, pp.1549-77, 2016.

H. F. Hu, W. W. Xu, Y. Wang, C. C. Zheng, W. X. Zhang et al., Comparative Proteomics Analysis Identifies Cdc42-Cdc42BPA Signaling as Prognostic Biomarker and Therapeutic Target for Colon Cancer Invasion, J Proteome Res, vol.17, issue.1, pp.265-75, 2018.

J. F. Huang, C. J. Wen, G. Z. Zhao, Y. Dai, Y. Li et al., Overexpression of ABCB4 contributes to acquired doxorubicin resistance in breast cancer cells in vitro, Cancer Chemother Pharmacol, vol.82, issue.2, pp.199-210, 2018.

L. Huang, A. Zhao, J. L. Lew, T. Zhang, Y. Hrywna et al., Farnesoid X receptor activates transcription of the phospholipid pump MDR3, J Biol Chem, vol.278, issue.51, pp.51085-90, 2003.

M. Hundt and S. John, Physiology, Bile Secretion. StatPearls. Treasure Island (FL), p.2019

Y. Ikebuchi, T. Takada, K. Ito, T. Yoshikado, N. Anzai et al., Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4, Hepatol Res, vol.39, issue.11, pp.1091-107, 2009.

Y. Ikeda, S. Y. Morita, R. Hatano, T. Tsuji, and T. Terada, Enhancing effect of taurohyodeoxycholate on ABCB4-mediated phospholipid efflux, Biochim Biophys Acta Mol Cell Biol Lipids, 2019.

N. Ikenaga, S. B. Liu, D. Y. Sverdlov, S. Yoshida, I. Nasser et al., A new Mdr2(-/-) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer, Am J Pathol, vol.185, issue.2, pp.325-359, 2015.

M. Ito, T. Nakano, F. Erdodi, and D. J. Hartshorne, Myosin phosphatase: structure, regulation and function, Mol Cell Biochem, vol.259, issue.1-2, pp.197-209, 2004.

T. Iwasaki, M. Murata-hori, S. Ishitobi, and H. Hosoya, Diphosphorylated MRLC is required for organization of stress fibers in interphase cells and the contractile ring in dividing cells, Cell Struct Funct, vol.26, issue.6, pp.677-83, 2001.

E. Jacquemin, Progressive familial intrahepatic cholestasis. Clinics and research in hepatology and gastroenterology, vol.36, pp.26-35, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01258764

E. Jacquemin, B. Hagenbuch, B. Stieger, A. W. Wolkoff, and P. J. Meier, Expression cloning of a rat liver Na(+)-independent organic anion transporter, Proc Natl Acad Sci, vol.91, issue.1, pp.133-140, 1994.

E. Jacquemin, D. Hermans, A. Myara, D. Habes, D. Debray et al., Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis, Hepatology, vol.25, issue.3, pp.519-542, 1997.

N. B. Javitt, History of hepatic bile formation: old problems, new approaches, Adv Physiol Educ, vol.38, issue.4, pp.279-85, 2014.

K. Y. Jih and T. C. Hwang, Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle, Proc Natl Acad Sci U S A, vol.110, issue.11, pp.4404-4413, 2013.

Y. S. Juan, S. M. Chuang, C. Y. Long, R. J. Lin, K. M. Liu et al., Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction, BJU Int, vol.110, issue.2, pp.283-92, 2012.

D. Jung, M. G. Elferink, F. Stellaard, and G. M. Groothuis, Analysis of bile acid-induced regulation of FXR target genes in human liver slices, Liver Int, vol.27, issue.1, pp.137-181, 2007.

D. Jung and G. A. Kullak-ublick, Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression, Hepatology, vol.37, issue.3, pp.622-653, 2003.

V. P. Kale, J. A. Hengst, D. H. Desai, T. E. Dick, K. N. Choe et al., A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion, Cancer Lett, vol.354, issue.2, pp.299-310, 2014.

M. Kano, J. Shoda, R. Sumazaki, K. Oda, Y. Nimura et al., Mutations identified in the human multidrug resistance P-glycoprotein 3 (ABCB4) gene in patients with primary hepatolithiasis, Hepatol Res, vol.29, issue.3, pp.160-166, 2004.

K. Kapoor, J. Bhatnagar, E. E. Chufan, and S. V. Ambudkar, Mutations in intracellular loops 1 and 3 lead to misfolding of human P-glycoprotein (ABCB1) that can be rescued by cyclosporine A, which reduces its association with chaperone Hsp70, J Biol Chem, vol.288, issue.45, pp.32622-32658, 2013.

S. J. Karpen, Nuclear receptor regulation of hepatic function, J Hepatol, vol.36, issue.6, pp.832-50, 2002.

K. Katayama, M. Yamaguchi, K. Noguchi, and Y. Sugimoto, Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function, Cancer Lett, vol.345, issue.1, pp.124-155, 2014.

K. N. Katayama, K. Sugimoto, and Y. , Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells, New Journal of Science, 2014.

K. Kawaguchi, M. Morita, . Abc-transporter, and D. Subfamily, Distinct Differences in Behavior between ABCD1-3 and ABCD4 in Subcellular Localization, Function, and Human Disease

, Biomed Res Int, p.6786245, 2016.

T. Kawamoto, G. Okano, and T. Akino, Biosynthesis and turnover of individual molecular species of phosphatidylcholine in liver and bile, Biochim Biophys Acta, vol.619, issue.1, pp.20-34, 1980.

D. Keating, G. Marigowda, L. Burr, C. Daines, M. A. Mall et al., VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles, N Engl J Med, vol.379, issue.17, pp.1612-1632, 2018.

R. Kellermayer, Translational readthrough induction of pathogenic nonsense mutations, Eur J Med Genet, vol.49, issue.6, pp.445-50, 2006.

E. Kerem, S. Hirawat, S. Armoni, Y. Yaakov, D. Shoseyov et al., Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial, Lancet, vol.372, issue.9640, pp.719-746, 2008.

E. Kerem, M. W. Konstan, D. Boeck, K. Accurso, F. J. Sermet-gaudelus et al., Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, doubleblind, placebo-controlled phase 3 trial, Lancet Respir Med, vol.2, issue.7, pp.539-586, 2014.

S. Kiehl, S. C. Herkt, A. M. Richter, L. Fuhrmann, N. El-nikhely et al., ABCB4 is frequently epigenetically silenced in human cancers and inhibits tumor growth, Sci Rep, vol.4, p.6899, 2014.

S. Kikuchi, M. Hata, K. Fukumoto, Y. Yamane, T. Matsui et al., Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes, Nat Genet, vol.31, issue.3, pp.320-325, 2002.

H. Kim, M. Barroso, R. Samanta, L. Greenberger, and E. Sztul, Experimentally induced changes in the endocytic traffic of P-glycoprotein alter drug resistance of cancer cells, Am J Physiol, vol.273, issue.2, pp.687-702, 1997.

Y. Kim and J. Chen, Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation, Science, vol.359, issue.6378, pp.915-924, 2018.

S. Kinting, S. Hoppner, U. Schindlbeck, M. E. Forstner, J. Harfst et al., Functional rescue of misfolding ABCA3 mutations by small molecular correctors, Hum Mol Genet, vol.27, issue.6, pp.943-53, 2018.

C. Kioussi, M. Appu, C. V. Lohr, K. A. Fischer, G. Bajaj et al., Co-expression of myosin II regulatory light chain and the NMDAR1 subunit in neonatal and adult mouse brain, Brain Res Bull, vol.74, issue.6, pp.439-51, 2007.

H. Kipp and I. M. Arias, Newly synthesized canalicular ABC transporters are directly targeted from the Golgi to the hepatocyte apical domain in rat liver, J Biol Chem, vol.275, issue.21, pp.15917-15942, 2000.

H. Kipp, N. Pichetshote, and I. M. Arias, Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver, J Biol Chem, vol.276, issue.10, pp.7218-7242, 2001.

C. D. Klaassen and L. M. Aleksunes, Xenobiotic, bile acid, and cholesterol transporters: function and regulation, Pharmacol Rev, vol.62, issue.1, pp.1-96, 2010.

O. Kocher, N. Comella, A. Gilchrist, R. Pal, K. Tognazzi et al., PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein, Lab Invest, vol.79, issue.9, pp.1161-70, 1999.

R. Kolling and S. Losko, The linker region of the ABC-transporter Ste6 mediates ubiquitination and fast turnover of the protein, EMBO J, vol.16, issue.9, pp.2251-61, 1997.

S. Koshiba, R. An, H. Saito, K. Wakabayashi, A. Tamura et al., Human ABC transporters ABCG2 (BCRP) and ABCG4, Xenobiotica, vol.38, issue.7-8, pp.863-88, 2008.

A. Kosters and S. J. Karpen, Bile acid transporters in health and disease, Xenobiotica, vol.38, issue.7-8, pp.1043-71, 2008.

M. Kovacs, F. Wang, A. Hu, Y. Zhang, and J. R. Sellers, Functional divergence of human cytoplasmic myosin II: kinetic characterization of the non-muscle IIA isoform, J Biol Chem, vol.278, issue.40, pp.38132-38172, 2003.

R. Kubitz, C. Huth, M. Schmitt, A. Horbach, G. Kullak-ublick et al., Protein kinase C-dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells, Hepatology, vol.34, issue.2, pp.340-50, 2001.

R. Kubitz, G. Sutfels, T. Kuhlkamp, R. Kolling, and D. Haussinger, Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase, Gastroenterology, vol.126, issue.2, pp.541-53, 2004.

A. K. Kurz, D. Graf, M. Schmitt, V. Dahl, S. Haussinger et al., Tauroursodesoxycholateinduced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats, Gastroenterology, vol.121, issue.2, pp.407-426, 2001.

P. Lam, S. Xu, C. J. Soroka, and J. L. Boyer, A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis, Hepatology, vol.55, issue.6, pp.1901-1912, 2012.

G. Lambert, B. Becker, R. Schreiber, A. Boucherot, M. Reth et al., Control of cystic fibrosis transmembrane conductance regulator expression by BAP31, J Biol Chem, vol.276, issue.23, pp.20340-20345, 2001.

G. Lambert and M. Krempf, Une maladie métabolique à l'origine de la découverte des transporteurs ABCG5 et ABCG8 modulant l'absorption intertinale du cholestérol, Médecine / Sciences, pp.815-821, 2001.

C. Lang, Y. Meier, B. Stieger, U. Beuers, T. Lang et al., Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury, Pharmacogenet Genomics, vol.17, issue.1, pp.47-60, 2007.

L. A. Lapierre, R. Kumar, C. M. Hales, J. Navarre, S. G. Bhartur et al., Myosin vb is associated with plasma membrane recycling systems, Mol Biol Cell, vol.12, issue.6, pp.1843-57, 2001.

I. C. Lee, T. Leung, and I. Tan, Adaptor protein LRAP25 mediates myotonic dystrophy kinaserelated Cdc42-binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin dynamics, J Biol Chem, vol.289, issue.39, pp.26989-7003, 2014.

L. A. Lee, A. Karabina, L. J. Broadwell, and L. A. Leinwand, The ancient sarcomeric myosins found in specialized muscles, Skelet Muscle, vol.9, issue.1, p.7, 2019.

K. Lefort, A. Mandinova, P. Ostano, V. Kolev, V. Calpini et al., Notch1 is a MRCKalpha kinases, Genes Dev, vol.21, issue.5, pp.562-77, 2007.

T. Leung, X. Q. Chen, I. Tan, E. Manser, and L. Lim, Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization, Mol Cell Biol, vol.18, issue.1, pp.130-170, 1998.

J. Li and P. A. Dawson, Animal models to study bile acid metabolism, Biochim Biophys Acta Mol Basis Dis, vol.1865, issue.5, pp.895-911, 2019.

L. Li, X. Wu, H. Y. Yue, Y. C. Zhu, and J. Xu, Myosin light chain kinase facilitates endocytosis of synaptic vesicles at hippocampal boutons, J Neurochem, vol.138, issue.1, pp.60-73, 2016.

M. Li, C. J. Soroka, K. Harry, and J. L. Boyer, CFTR-associated ligand is a negative regulator of Mrp2 expression, Am J Physiol Cell Physiol, vol.312, issue.1, pp.40-46, 2017.

M. Li, W. Wang, C. J. Soroka, A. Mennone, K. Harry et al., NHERF-1 binds to Mrp2 and regulates hepatic Mrp2 expression and function, J Biol Chem, vol.285, issue.25, pp.19299-307, 2010.

N. Li, Z. Cui, F. Fang, J. Y. Lee, and N. Ballatori, Heterodimerization, trafficking and membrane topology of the two proteins, Ost alpha and Ost beta, that constitute the organic solute and steroid transporter, Biochem J, vol.407, issue.3, pp.363-72, 2007.

Z. Li, L. B. Agellon, and D. E. Vance, Phosphatidylcholine homeostasis and liver failure, J Biol Chem, vol.280, issue.45, pp.37798-802, 2005.

Z. Li, L. B. Agellon, and D. E. Vance, The role of phosphatidylethanolamine methyltransferase in a mouse model of intrahepatic cholestasis, Biochim Biophys Acta, vol.1811, issue.4, pp.278-83, 2011.

C. R. Lincke, J. J. Smit, T. Van-der-velde-koerts, and P. Borst, Structure of the human MDR3 gene and physical mapping of the human MDR locus, J Biol Chem, vol.266, issue.8, pp.5303-5313, 1991.

V. Ling, Drug resistance and membrane alteration in mutants of mammalian cells, Can J Genet Cytol, vol.17, issue.4, pp.503-518, 1975.

K. J. Linton, Structure and function of ABC transporters, Physiology (Bethesda), vol.22, pp.122-152, 2007.

Y. Liu, J. Binz, M. J. Numerick, S. Dennis, G. Luo et al., Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra-and extrahepatic cholestasis, J Clin Invest, vol.112, issue.11, pp.1678-87, 2003.

K. P. Locher, Mechanistic diversity in ATP-binding cassette (ABC) transporters, Nat Struct Mol Biol, vol.23, issue.6, pp.487-93, 2016.

H. I. Lowe, C. T. Watson, S. Badal, N. J. Toyang, and J. Bryant, Cycloartane-3,24,25-triol inhibits MRCKalpha kinase and demonstrates promising anti prostate cancer activity in vitro, Cancer Cell Int, vol.12, issue.1, p.46, 2012.

E. Lozano, O. Briz, R. Macias, M. A. Serrano, J. Marin et al., Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition, J Pers Med, vol.8, issue.2, 2018.

T. T. Lu, M. Makishima, J. J. Repa, K. Schoonjans, T. A. Kerr et al., Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors, Mol Cell, vol.6, issue.3, pp.507-522, 2000.

S. Macalou, R. W. Robey, J. Gozzi, G. Shukla, S. Grosjean et al., The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport, Cell Mol Life Sci, vol.73, issue.9, pp.1927-1964, 2016.

D. Madenci and S. U. Egelhaaf, Self-assembly in aqueous bile salt solutions, Curr Opin Colloid In, vol.15, issue.1-2, pp.109-124, 2010.

J. Maldonado-valderrama, P. Wilde, A. Macierzanka, and A. Mackie, The role of bile salts in digestion, Adv Colloid Interface Sci, vol.165, issue.1, pp.36-46, 2011.

M. A. Mall and D. N. Sheppard, Chronic ivacaftor treatment: getting F508del-CFTR into more trouble?, J Cyst Fibros, vol.13, issue.6, pp.605-612, 2014.

V. Marigo, A. Nigro, A. Pecci, D. Montanaro, D. Stazio et al., Correlation between the clinical phenotype of MYH9-related disease and tissue distribution of class II nonmuscle myosin heavy chains, Genomics, vol.83, issue.6, pp.1125-1158, 2004.

V. Mariotti, M. Strazzabosco, L. Fabris, and D. F. Calvisi, Animal models of biliary injury and altered bile acid metabolism, Biochim Biophys Acta Mol Basis Dis, vol.1864, issue.4, pp.1254-61, 2018.

O. B. Matas, J. A. Martinez-menarguez, and G. Egea, Association of Cdc42/N-WASP/Arp2/3 signaling pathway with Golgi membranes, Traffic, vol.5, issue.11, pp.838-884, 2004.

E. Matthes, J. Goepp, G. W. Carlile, Y. Luo, K. Dejgaard et al., Low free drug concentration prevents inhibition of F508del CFTR functional expression by the potentiator VX-770 (ivacaftor), Br J Pharmacol, vol.173, issue.3, pp.459-70, 2016.

T. H. Mauad, C. M. Van-nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel et al., Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis, Am J Pathol, vol.145, issue.5, pp.1237-1282, 1994.

P. Melin, V. Thoreau, C. Norez, F. Bilan, A. Kitzis et al., The cystic fibrosis mutation G1349D within the signature motif LSHGH of NBD2 abolishes the activation of CFTR chloride channels by genistein, Biochem Pharmacol, vol.67, issue.12, pp.2187-96, 2004.

A. E. Mengesha and P. M. Bummer, Simple chromatographic method for simultaneous analyses of phosphatidylcholine, lysophosphatidylcholine, and free fatty acids, AAPS PharmSciTech, vol.11, issue.3, pp.1084-91, 2010.

S. Misra, P. Ujhazy, Z. Gatmaitan, L. Varticovski, and I. M. Arias, The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP-dependent canalicular transporters in rat liver, J Biol Chem, vol.273, issue.41, pp.26638-26682, 1998.

S. Misra, P. Ujhazy, L. Varticovski, and I. M. Arias, Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles, Proc Natl Acad Sci, vol.96, issue.10, pp.5814-5823, 1999.

S. Misra, L. Varticovski, and I. M. Arias, Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles, Am J Physiol Gastrointest Liver Physiol, vol.285, issue.2, pp.316-340, 2003.

S. Y. Morita, A. Kobayashi, Y. Takanezawa, N. Kioka, T. Handa et al., Bile saltdependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4, Hepatology, vol.46, issue.1, pp.188-99, 2007.

A. Musch, The unique polarity phenotype of hepatocytes, Exp Cell Res, vol.328, issue.2, pp.276-83, 2014.

H. Nakagawa, A. Tamura, K. Wakabayashi, K. Hoshijima, M. Komada et al., Ubiquitin-mediated proteasomal degradation of non-synonymous SNP variants of human ABC transporter ABCG2, Biochem J, vol.411, issue.3, pp.623-654, 2008.

H. Nakagawa, Y. Toyoda, K. Wakabayashi-nakao, H. Tamaki, M. Osumi et al., Ubiquitin-mediated proteasomal degradation of ABC transporters: a new aspect of genetic polymorphisms and clinical impacts, J Pharm Sci, vol.100, issue.9, pp.3602-3621, 2011.

H. Nakagawa, K. Wakabayashi-nakao, A. Tamura, Y. Toyoda, S. Koshiba et al., Disruption of N-linked glycosylation enhances ubiquitin-mediated proteasomal degradation of the human ATP-binding cassette transporter ABCG2, FEBS J, vol.276, issue.24, pp.7237-52, 2009.

S. Nakagawa, I. Makino, T. Ishizaki, and I. Dohi, Dissolution of cholesterol gallstones by ursodeoxycholic acid, Lancet, vol.2, issue.8034, pp.367-376, 1977.

S. Naoi, H. Hayashi, T. Inoue, K. Tanikawa, K. Igarashi et al., Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2, J Pediatr, vol.164, issue.5, pp.1219-1246, 2014.

A. C. Nathwani, U. M. Reiss, E. G. Tuddenham, C. Rosales, P. Chowdary et al., Long-term safety and efficacy of factor IX gene therapy in hemophilia B, N Engl J Med, vol.371, issue.21, pp.1994-2004, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02881140

V. Nemcova-furstova, D. Kopperova, K. Balusikova, M. Ehrlichova, V. Brynychova et al., Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters, Toxicol Appl Pharmacol, vol.310, pp.215-243, 2016.

K. A. Newell-litwa, R. Horwitz, and M. L. Lamers, Non-muscle myosin II in disease: mechanisms and therapeutic opportunities, Dis Model Mech, vol.8, issue.12, pp.1495-515, 2015.

Y. Ng, I. Tan, L. Lim, and T. Leung, Expression of the human myotonic dystrophy kinase-related Cdc42-binding kinase gamma is regulated by promoter DNA methylation and Sp1 binding, J Biol Chem, vol.279, issue.33, pp.34156-64, 2004.

M. Nicolaou, E. J. Andress, J. K. Zolnerciks, P. H. Dixon, C. Williamson et al., Canalicular ABC transporters and liver disease, J Pathol, vol.226, issue.2, pp.300-315, 2012.

C. Norez, S. Noel, M. Wilke, M. Bijvelds, H. Jorna et al., Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat, FEBS Lett, vol.580, issue.8, pp.2081-2087, 2006.

C. Norez, C. Vandebrouck, J. Bertrand, S. Noel, E. Durieu et al., Roscovitine is a proteostasis regulator that corrects the trafficking defect of F508del-CFTR by a CDKindependent mechanism, Br J Pharmacol, vol.171, issue.21, pp.4831-4880, 2014.

V. P. O'brien, K. Bokelmann, J. Ramirez, K. Jobst, M. J. Ratain et al.,

I. Park, C. Han, J. S. Lee, B. Choi, H. Kwon et al., Myosin regulatory light chains are required to maintain the stability of myosin II and cellular integrity, Biochem J, vol.434, issue.1, pp.171-80, 2011.

S. W. Park, C. M. Schonhoff, C. R. Webster, and M. S. Anwer, Protein kinase Cdelta differentially regulates cAMP-dependent translocation of NTCP and MRP2 to the plasma membrane, Am J Physiol Gastrointest Liver Physiol, vol.303, issue.5, pp.657-65, 2012.

E. Pasmant, P. Goussard, L. Baranes, I. Laurendeau, S. Quentin et al., First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis, Eur J Hum Genet, vol.20, issue.3, pp.277-82, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00685384

C. C. Paulusma, A. Groen, C. Kunne, K. S. Ho-mok, A. L. Spijkerboer et al., Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport, Hepatology, vol.44, issue.1, pp.195-204, 2006.

G. Paumgartner and U. Beuers, Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited, Hepatology, vol.36, issue.3, pp.525-556, 2002.

S. Paytubi, N. A. Morrice, J. Boudeau, and C. G. Proud, The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2, Biochem J, vol.409, issue.1, pp.223-254, 2008.

A. Pecci, X. Ma, A. Savoia, and R. S. Adelstein, MYH9: Structure, functions and role of nonmuscle myosin IIA in human disease, Gene, vol.664, pp.152-67, 2018.

L. A. Perkins, G. W. Fisher, M. Naganbabu, B. F. Schmidt, F. Mun et al., High-Content Surface and Total Expression siRNA Kinase Library Screen with VX-809 Treatment Reveals Kinase Targets that Enhance F508del-CFTR Rescue, Mol Pharm, vol.15, issue.3, pp.759-67, 2018.

E. Perland and R. Fredriksson, Classification Systems of Secondary Active Transporters, Trends Pharmacol Sci, vol.38, issue.3, pp.305-320, 2017.

M. Podda, C. Ghezzi, P. M. Battezzati, E. Bertolini, A. Crosignani et al., Effect of different doses of ursodeoxycholic acid in chronic liver disease, Dig Dis Sci, vol.34, issue.12, pp.59-65, 1989.

Y. Popov, E. Patsenker, P. Fickert, M. Trauner, and D. Schuppan, Mdr2 (Abcb4)-/-mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro-and antifibrogenic genes, J Hepatol, vol.43, issue.6, pp.1045-54, 2005.

I. Portal, T. Clerc, V. Sbarra, H. Portugal, A. M. Pauli et al., Importance of highdensity lipoprotein-phosphatidylcholine in secretion of phospholipid and cholesterol in bile, Am J Physiol, vol.264, issue.6, pp.1052-1058, 1993.

P. Portincasa and G. Calamita, Water channel proteins in bile formation and flow in health and disease: when immiscible becomes miscible, Mol Aspects Med, vol.33, issue.5-6, pp.651-64, 2012.

I. Pranke, L. Bidou, N. Martin, S. Blanchet, A. Hatton et al., Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons, ERJ Open Res, vol.4, issue.1, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02145353

N. Presa, R. D. Clugston, S. Lingrell, S. E. Kelly, A. H. Merrill et al., Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice, Biochim Biophys Acta Mol Basis Dis, vol.1865, issue.1, pp.14-25, 2019.

L. S. Prince, K. Peter, S. R. Hatton, L. Zaliauskiene, L. F. Cotlin et al., Efficient endocytosis of the cystic fibrosis transmembrane conductance regulator requires a tyrosinebased signal, J Biol Chem, vol.274, issue.6, pp.3602-3611, 1999.

E. M. Quistgaard, C. Low, P. Moberg, F. Guettou, K. Maddi et al., Structural and biophysical characterization of the cytoplasmic domains of human BAP29 and BAP31, PLoS One, vol.8, issue.8, p.71111, 2013.

P. S. Rao, U. Bickel, K. S. Srivenugopal, and U. S. Rao, Bap29varP, a variant of Bap29, influences the cell surface expression of the human P-glycoprotein, Int J Oncol, vol.32, issue.1, pp.135-179, 2008.

M. Raymond, E. Rose, D. E. Housman, and P. Gros, Physical mapping, amplification, and overexpression of the mouse mdr gene family in multidrug-resistant cells, Mol Cell Biol, vol.10, issue.4, pp.1642-51, 1990.

J. Reardon, T. Hussaini, M. Alsahafi, V. M. Azalgara, S. R. Erb et al.,

, Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review, J Clin Transl Hepatol, vol.4, issue.3, pp.192-205, 2016.

V. I. Reshetnyak, Physiological and molecular biochemical mechanisms of bile formation, World J Gastroenterol, vol.19, issue.42, pp.7341-60, 2013.

M. Rius, J. Hummel-eisenbeiss, A. F. Hofmann, and D. Keppler, Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione, Am J Physiol Gastrointest Liver Physiol, vol.290, issue.4, pp.640-649, 2006.

H. Roelofsen, C. J. Soroka, D. Keppler, and J. L. Boyer, Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets, J Cell Sci, vol.111, pp.1137-1182, 1998.

R. Rojas, W. G. Ruiz, S. M. Leung, T. S. Jou, and G. Apodaca, Cdc42-dependent modulation of tight junctions and membrane protein traffic in polarized Madin-Darby canine kidney cells, Mol Biol Cell, vol.12, issue.8, pp.2257-74, 2001.

M. G. Roma, P. Milkiewicz, E. Elias, and R. Coleman, Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: role of the cytoskeleton, Hepatology, vol.32, issue.6, pp.1342-56, 2000.

O. Rosmorduc, B. Hermelin, and R. Poupon, MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis, Gastroenterology, vol.120, issue.6, pp.1459-67, 2001.

O. Rosmorduc and R. Poupon, Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene, Orphanet J Rare Dis, vol.2, p.29, 2007.

D. Rost, J. Kartenbeck, and D. Keppler, Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis, Hepatology, vol.29, issue.3, pp.814-835, 1999.

R. C. Rubenstein, M. E. Egan, and P. L. Zeitlin, In vitro pharmacologic restoration of CFTRmediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR, J Clin Invest, vol.100, issue.10, pp.2457-65, 1997.

S. Ruetz and P. Gros, Phosphatidylcholine translocase: a physiological role for the mdr2 gene, Cell, vol.77, issue.7, pp.1071-81, 1994.

D. W. Russell, The enzymes, regulation, and genetics of bile acid synthesis, Annu Rev Biochem, vol.72, pp.137-74, 2003.

D. W. Russell, Fifty years of advances in bile acid synthesis and metabolism, J Lipid Res, vol.50, pp.120-125, 2009.

I. Sabirzhanova, L. Pacheco, M. Rapino, D. Grover, R. Handa et al., Rescuing Trafficking Mutants of the ATP-binding Cassette Protein, ABCA4, with Small Molecule Correctors as a Treatment for Stargardt Eye Disease, J Biol Chem, vol.290, issue.32, pp.19743-55, 2015.

T. Saeki, K. Ueda, Y. Tanigawara, R. Hori, and T. Komano, Human P-glycoprotein transports cyclosporin A and FK506, J Biol Chem, vol.268, issue.9, pp.6077-80, 1993.

Y. Sai, A. T. Nies, and I. M. Arias, Bile acid secretion and direct targeting of mdr1-green fluorescent protein from Golgi to the canalicular membrane in polarized WIF-B cells, J Cell Sci, vol.112, pp.4535-4580, 1999.

M. Sambrotta and R. J. Thompson, Mutations in TJP2, encoding zona occludens 2, and liver disease, Tissue Barriers, vol.3, issue.3, p.1026537, 2015.

M. J. Schell, M. Maurice, B. Stieger, and A. L. Hubbard, 5'nucleotidase is sorted to the apical domain of hepatocytes via an indirect route, J Cell Biol, vol.119, issue.5, pp.1173-82, 1992.

A. H. Schinkel, S. Kemp, M. Dolle, G. Rudenko, and E. Wagenaar, N-glycosylation and deletion mutants of the human MDR1 P-glycoprotein, J Biol Chem, vol.268, issue.10, pp.7474-81, 1993.

B. M. Schroeder and M. , Endocytosis as an essential process in liver function and pathology, The Liver Biology and Pathobiology, 2009.

I. Sermet-gaudelus, K. D. Boeck, G. J. Casimir, F. Vermeulen, T. Leal et al.,

, Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis, Am J Respir Crit Care Med, vol.182, issue.10, pp.1262-72, 2010.

A. Sharanek, A. Burban, M. Burbank, L. Guevel, R. Li et al., Rhokinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs, Sci Rep, vol.6, p.24709, 2016.

B. Shi, S. Li, H. Ju, X. Liu, D. Li et al., Protein kinase C inhibitor chelerythrine attenuates partial unilateral ureteral obstruction induced kidney injury in neonatal rats, Life Sci, vol.216, pp.85-91, 2019.

B. Short, The first buds of Cdc42, J Cell Biol, vol.209, issue.6, p.780, 2015.

M. S. Shutova and T. M. Svitkina, Common and Specific Functions of Nonmuscle Myosin II Paralogs in Cells, Biochemistry (Mosc), vol.83, issue.12, pp.1459-68, 2018.

S. M. Siew, S. C. Cunningham, E. Zhu, S. S. Tay, E. Venuti et al., Prevention of cholestatic liver disease and reduced tumorigenicity in a murine model of PFIC type 3 using hybrid AAV-piggyBac gene therapy, Hepatology, 2019.

R. R. Singaraja, M. H. Kang, K. Vaid, S. S. Sanders, G. L. Vilas et al., Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function, Circ Res, vol.105, issue.2, pp.138-185, 2009.

T. M. Sissung, J. Deeken, C. R. Leibrand, D. K. Price, S. Ehrlich et al., Identification of novel SNPs associated with risk and prognosis in patients with castrationresistant prostate cancer, Pharmacogenomics, vol.17, issue.18, pp.1979-86, 2016.

T. A. Slimane, G. Trugnan, I. Van, and D. Hoekstra, Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains, Mol Biol Cell, vol.14, issue.2, pp.611-635, 2003.

J. J. Smit, A. H. Schinkel, C. A. Mol, D. Majoor, W. J. Mooi et al., Tissue distribution of the human MDR3 P-glycoprotein, Lab Invest, vol.71, issue.5, pp.638-687, 1994.

A. Smith, V. Imperio, E. Ajello, F. Ferrario, N. Mosele et al., The putative role of MALDI-MSI in the study of Membranous Nephropathy, Biochim Biophys Acta, vol.1865, issue.7, pp.865-74, 2017.

A. J. Smith, J. M. De-vree, R. Ottenhoff, O. Elferink, R. P. Schinkel et al., Hepatocytespecific expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice, Hepatology, vol.28, issue.2, pp.530-536, 1998.

A. J. Smith, A. Van-helvoort, G. Van-meer, K. Szabo, E. Welker et al., MDR3 Pglycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping, J Biol Chem, vol.275, issue.31, pp.23530-23539, 2000.

T. Sumi, K. Matsumoto, A. Shibuya, and T. Nakamura, Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha, J Biol Chem, vol.276, issue.25, pp.23092-23098, 2001.

V. Sundaram and E. S. Bjornsson, Drug-induced cholestasis, Hepatol Commun, vol.1, issue.8, pp.726-761, 2017.

M. Symons and N. Rusk, Control of vesicular trafficking by Rho GTPases, Curr Biol, vol.13, issue.10, pp.409-427, 2003.

Z. J. Talaga and P. N. Vaidya, Dubin Johnson Syndrome. StatPearls. Treasure Island, p.2019

H. J. Tan, M. Deng, J. W. Qiu, J. F. Wu, and Y. Z. Song, Monozygotic Twins Suffering From Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report, Front Pediatr, vol.6, p.354, 2018.

I. Tan, A. Cheong, L. Lim, and T. Leung, Genomic organization of human myotonic dystrophy kinase-related Cdc42-binding kinase alpha reveals multiple alternative splicing and functional diversity, Gene, vol.304, pp.107-122, 2003.

I. Tan, C. H. Ng, L. Lim, and T. Leung, Phosphorylation of a novel myosin binding subunit of protein phosphatase 1 reveals a conserved mechanism in the regulation of actin cytoskeleton, J Biol Chem, vol.276, issue.24, pp.21209-21225, 2001.

I. Tan, J. Yong, J. M. Dong, L. Lim, and T. Leung, A tripartite complex containing MRCK modulates lamellar actomyosin retrograde flow, Cell, vol.135, issue.1, pp.123-159, 2008.

J. L. Taylor-cousar, M. A. Mall, B. W. Ramsey, E. F. Mckone, E. Tullis et al., Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles, ERJ Open Res, vol.5, issue.2, 2019.

J. L. Taylor-cousar, A. Munck, E. F. Mckone, C. K. Van-der-ent, A. Moeller et al., Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del, N Engl J Med, vol.377, issue.21, pp.2013-2036, 2017.

C. Thomas, R. Pellicciari, M. Pruzanski, J. Auwerx, and K. Schoonjans, Targeting bile-acid signalling for metabolic diseases, Nat Rev Drug Discov, vol.7, issue.8, pp.678-93, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00311230

T. Trajkovska, K. Topuzovska, and S. , High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol, Anatol J Cardiol, vol.18, issue.2, pp.149-54, 2017.

D. Tougeron, G. Fotsing, V. Barbu, and M. Beauchant, ABCB4/MDR3 gene mutations and cholangiocarcinomas, J Hepatol, vol.57, issue.2, pp.467-475, 2012.

A. Treyer and A. Musch, Hepatocyte polarity, Compr Physiol, vol.3, issue.1, pp.243-87, 2013.

M. Unbekandt, S. Belshaw, J. Bower, M. Clarke, J. Cordes et al., Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer, Cancer Res, vol.78, issue.8, pp.2096-114, 2018.

M. Unbekandt, D. R. Croft, D. Crighton, M. Mezna, D. Mcarthur et al., A novel small-molecule MRCK inhibitor blocks cancer cell invasion, Cell Commun Signal, vol.12, p.54, 2014.

M. Unbekandt and M. F. Olson, The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer, J Mol Med (Berl), vol.92, issue.3, pp.217-242, 2014.

A. M. Van-der-bliek, F. Baas, T. Houte-de-lange, T. Kooiman, P. M. Van-der-velde-koerts et al., The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver, EMBO J, vol.6, issue.11, pp.3325-3356, 1987.

F. Van-goor, S. Hadida, P. D. Grootenhuis, B. Burton, D. Cao et al., Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770, Proc Natl Acad Sci, vol.106, issue.44, pp.18825-18855, 2009.

F. Van-goor, K. S. Straley, D. Cao, J. Gonzalez, S. Hadida et al., Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules, Am J Physiol Lung Cell Mol Physiol, vol.290, issue.6, pp.1117-1147, 2006.

A. Van-helvoort, A. J. Smith, H. Sprong, I. Fritzsche, A. H. Schinkel et al., MDR1 Pglycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine, Cell, vol.87, issue.3, pp.507-524, 1996.

J. Van-hengel, D. 'hooge, P. Hooghe, B. Wu, X. Libbrecht et al., Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver, Gastroenterology, vol.134, issue.3, pp.781-92, 2008.

D. E. Vance, Physiological roles of phosphatidylethanolamine N-methyltransferase

, Biochim Biophys Acta, vol.1831, issue.3, pp.626-658, 2013.

J. E. Vance, T. M. Nguyen, and D. E. Vance, The biosynthesis of phosphatidylcholine by methylation of phosphatidylethanolamine derived from ethanolamine is not required for lipoprotein secretion by cultured rat hepatocytes, Biochim Biophys Acta, vol.875, issue.3, pp.501-510, 1986.

V. Vauthier, B. Saad, A. Elie, J. Oumata, N. Durand-schneider et al., Structural analogues of roscovitine rescue the intracellular traffic and the function of ERretained ABCB4 variants in cell models, Sci Rep, vol.9, issue.1, p.6653, 2019.

V. Vauthier, C. Housset, and T. Falguieres, Targeted pharmacotherapies for defective ABC transporters, Biochem Pharmacol, vol.136, pp.1-11, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01482176

F. M. Vaz, C. C. Paulusma, H. Huidekoper, M. De-ru, C. Lim et al., Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype, Hepatology, vol.61, issue.1, pp.260-267, 2015.

R. Vazhappilly, K. S. Wee, N. J. Sucher, and C. M. Low, A non-muscle myosin II motor links NR1 to retrograde trafficking and proteasomal degradation in PC12 cells, Neurochem Int, vol.56, issue.4, pp.569-76, 2010.

G. Veit, R. G. Avramescu, A. N. Chiang, S. A. Houck, Z. Cai et al., From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations

, Mol Biol Cell, vol.27, issue.3, pp.424-457, 2016.

G. Veit, R. G. Avramescu, D. Perdomo, P. W. Phuan, M. Bagdany et al., Some gating potentiators, including VX-770, diminish DeltaF508-CFTR functional expression, Sci Transl Med, vol.6, issue.246, pp.246-97, 2014.

G. Veit, H. Xu, E. Dreano, R. G. Avramescu, M. Bagdany et al., Structure-guided combination therapy to potently improve the function of mutant CFTRs, Nat Med, vol.24, issue.11, pp.1732-1774, 2018.

M. Vicente-manzanares, X. Ma, R. S. Adelstein, and A. R. Horwitz, Non-muscle myosin II takes centre stage in cell adhesion and migration, Nat Rev Mol Cell Biol, vol.10, issue.11, pp.778-90, 2009.

Y. Wakabayashi, P. Dutt, J. Lippincott-schwartz, and I. M. Arias, Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells, Proc Natl Acad Sci, vol.102, issue.42, pp.15087-92, 2005.

Y. Wakabayashi, J. Lippincott-schwartz, and I. M. Arias, Intracellular trafficking of bile salt export pump (ABCB11) in polarized hepatic cells: constitutive cycling between the canalicular membrane and rab11-positive endosomes, Mol Biol Cell, vol.15, issue.7, pp.3485-96, 2004.

Y. A. Wakabayashi and I. M. , Apical recycling of Canalicular ABC Transporters, The Liver Biology and Pathobiology, vol.56, p.349, 2009.

K. Wakabayashi-nakao, A. Tamura, T. Furukawa, H. Nakagawa, and T. Ishikawa, Quality control of human ABCG2 protein in the endoplasmic reticulum: ubiquitination and proteasomal degradation, Adv Drug Deliv Rev, vol.61, issue.1, pp.66-72, 2009.

S. Wan, F. Kuipers, R. Havinga, H. Ando, D. E. Vance et al., Impaired Hepatic Phosphatidylcholine Synthesis Leads to Cholestasis in Mice Challenged With a High-Fat Diet, Hepatol Commun, vol.3, issue.2, pp.262-76, 2019.

Y. Wang, T. W. Loo, M. C. Bartlett, and D. M. Clarke, Modulating the folding of P-glycoprotein and cystic fibrosis transmembrane conductance regulator truncation mutants with pharmacological chaperones, Mol Pharmacol, vol.71, issue.3, pp.751-759, 2007.

J. R. Watson, D. Owen, and H. R. Mott, Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover, Small GTPases, vol.8, issue.4, pp.237-281, 2017.

E. M. Welch, E. R. Barton, J. Zhuo, Y. Tomizawa, W. J. Friesen et al., PTC124 targets genetic disorders caused by nonsense mutations, Nature, vol.447, issue.7140, pp.87-91, 2007.

S. Wilkinson, H. F. Paterson, and C. J. Marshall, Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion, Nat Cell Biol, vol.7, issue.3, pp.255-61, 2005.

M. Wilschanski, C. Famini, H. Blau, J. Rivlin, A. Augarten et al., A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations, Am J Respir Crit Care Med, vol.161, issue.3, pp.860-865, 2000.

M. Wilschanski, L. L. Miller, D. Shoseyov, H. Blau, J. Rivlin et al., Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis, Eur Respir J, vol.38, issue.1, pp.59-69, 2011.

K. A. Wojtal, E. De-vries, D. Hoekstra, and S. C. Van-ijzendoorn, Efficient trafficking of MDR1/Pglycoprotein to apical canalicular plasma membranes in HepG2 cells requires PKA-RIIalpha anchoring and glucosylceramide, Mol Biol Cell, vol.17, issue.8, pp.3638-50, 2006.

A. Woods, A. J. Heslegrave, P. J. Muckett, A. P. Levene, M. Clements et al., LKB1 is required for hepatic bile acid transport and canalicular membrane integrity in mice, Biochem J, vol.434, issue.1, pp.49-60, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00560694

O. M. Woodward, A. Kottgen, and M. Kottgen, ABCG transporters and disease, FEBS J, vol.278, issue.18, pp.3215-3240, 2011.

O. M. Woodward, D. N. Tukaye, J. Cui, P. Greenwell, L. M. Constantoulakis et al., Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules, Proc Natl Acad Sci, vol.110, issue.13, pp.5223-5231, 2013.

C. Xie, N. Li, Z. J. Chen, B. L. Li, and B. L. Song, The small GTPase Cdc42 interacts with Niemann-Pick C1-like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol-dependent manner, J Biol Chem, vol.286, issue.41, pp.35933-35975, 2011.

Y. Xie, M. Burcu, D. E. Linn, Y. Qiu, and M. R. Baer, Pim-1 kinase protects P-glycoprotein from degradation and enables its glycosylation and cell surface expression, Mol Pharmacol, vol.78, issue.2, pp.310-318, 2010.

H. I. Yeh, Y. Sohma, K. Conrath, and T. C. Hwang, A common mechanism for CFTR potentiators

, J Gen Physiol, vol.149, issue.12, pp.1105-1123, 2017.

H. Yu, B. Burton, C. J. Huang, J. Worley, D. Cao et al., Ivacaftor potentiation of multiple CFTR channels with gating mutations, J Cyst Fibros, vol.11, issue.3, pp.237-282, 2012.

L. Yu, R. E. Hammer, J. Li-hawkins, V. Bergmann, K. Lutjohann et al., Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion, Proc Natl Acad Sci, vol.99, issue.25, pp.16237-16279, 2002.

H. Yuan, H. Zhang, X. Wu, Z. Zhang, D. Du et al., Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice, Hepatology, vol.49, issue.1, pp.240-249, 2009.

S. Zanlungo, A. Rigotti, and F. Nervi, Hepatic cholesterol transport from plasma into bile: implications for gallstone disease, Curr Opin Lipidol, vol.15, issue.3, pp.279-86, 2004.

Q. Zhang, W. Yang, H. Song, H. Wu, Y. Lu et al., Tissue distribution and ontogeny of multidrug resistance protein 2, a phosphatidylcholine translocator, in rats, Eur J Drug Metab Pharmacokinet, vol.41, issue.1, pp.87-91, 2016.

Z. Zhang, F. Liu, and J. Chen, Conformational Changes of CFTR upon Phosphorylation and ATP Binding, Cell, vol.170, issue.3, pp.483-91, 2017.

Z. Zhang, J. Y. Wu, W. N. Hait, and J. M. Yang, Regulation of the stability of P-glycoprotein by ubiquitination, Mol Pharmacol, vol.66, issue.3, pp.395-403, 2004.

Z. Zhao and E. Manser, Myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK), the ROCK-like effectors of Cdc42 and Rac1, Small GTPases, vol.6, issue.2, pp.81-89, 2015.

Z. S. Zhao and E. Manser, PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation, Biochem J, vol.386, issue.2, pp.201-215, 2005.

C. Zhou, S. Verma, and B. Blumberg, The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism, Nucl Recept Signal, vol.7, p.1, 2009.

X. Zhu, J. Song, M. H. Mar, L. J. Edwards, and S. H. Zeisel, Phosphatidylethanolamine Nmethyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline, Biochem J, vol.370, pp.987-93, 2003.

J. Zielenski and L. C. Tsui, Cystic fibrosis: genotypic and phenotypic variations, Annu Rev Genet, vol.29, pp.777-807, 1995.

M. Ziol, V. Barbu, O. Rosmorduc, A. Frassati-biaggi, N. Barget et al., ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults, Gastroenterology, vol.135, issue.1, pp.131-172, 2008.

G. Zollner and M. Trauner, Nuclear receptors as therapeutic targets in cholestatic liver diseases, Br J Pharmacol, vol.156, issue.1, pp.7-27, 2009.

G. Zollner, M. Wagner, T. Moustafa, P. Fickert, D. Silbert et al., Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids, Am J Physiol Gastrointest Liver Physiol, vol.290, issue.5, pp.923-955, 2006.

A. E. Zucchetti, I. R. Barosso, A. Boaglio, J. M. Pellegrino, E. J. Ochoa et al., Prevention of estradiol 17beta-D-glucuronide-induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes, Mol Biol Cell, vol.22, issue.20, pp.3902-3917, 2011.