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Les protéines Gα12 et Gα13 dans la mucoviscidose : Rôle dans la dégradation de la protéine CFTR mutée F508del et dans le contrôle des jonctions intercellulaires.

Abstract : F508del, the most frequent mutation found in cystic fibrosis (CF) population, impacts CFTR (Cystic Fibrosis Transmembrane conductance Regulator) trafficking and causes its rapid degradation at the endoplasmic compartment, resulting in a significant decrease in Cl- secretion at the apical membrane of epithelial cells. F508del has two main features, significant thickening of the bronchial mucus and a reduction in the integrity of the luminal barrier of the bronchial epithelium. These two phenomena are involved in the invasion and infection of lung tissue by pathogenic bacteria such as Pseudomonas aeruginosa, exacerbating the inflammation and lung destruction. The objective of this study was to determine the role of two proteins member of the heterotrimeric G proteins family, G12 and G13, in the degradation of the F508del CFTR, and in the control of junctional complexes in the normal and CF bronchial epithelium. Our results show for the first time that G12 and G13 are down expressed in CF. G12, but not G13, is involved in the control of F508del-CFTR degradation through its interaction with Calnexin and HSP90 chaperones. Unlike kidney epithelia cells, G12 promotes the formation and maintenance of cell junctions in the bronchial epithelium by affecting E-cadherine and ZO-1 stability. Altogether, our results set therefore G12 as a significant actor of the CF disease.
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https://tel.archives-ouvertes.fr/tel-00684255
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Sylvain Chauvet. Les protéines Gα12 et Gα13 dans la mucoviscidose : Rôle dans la dégradation de la protéine CFTR mutée F508del et dans le contrôle des jonctions intercellulaires.. Sciences agricoles. Université de Grenoble, 2011. Français. ⟨NNT : 2011GRENV082⟩. ⟨tel-00684255⟩

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