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Membrane binding properties of RAB GTPases

Abstract : RAB GTPases are major regulators of vesicular trafficking and localize to specific compartments. Deciphering the molecular mechanisms governing RAB localization is thus critical to understand intracellular transport processes. We have managed, for the first time, to incorporate purified and prenylated RABs into artificial membranes. By doing so, we observed that RAB6, but not RAB1 or RAB5, is able to promote by itself vesicle tethering. We believe that RAB6 is able to interact in trans with itself and to consequently drive homotypic membrane tethering. In the main part of this study, we investigated the physicochemical membrane requirements necessary for RAB recruitment. RAB1, RAB5 and RAB6 were all found to only localize to disordered membrane domains and to preferentially bind to curved membranes. We demonstrated that this specific recruitment of RAB1, RAB5 and RAB6 is primarily dependent on the hydrophobic insertion of their prenyl group into lipid packing defects. In contrast, RAB35 recruitment was primarily dependent on the presence of negatively charged lipids and was found to be modulated, to a lesser extent, by lipid packing defects. Although RAB4 and RAB11 were effectively recruited to purified Golgi fractions, in an effector-independent manner, membrane charges and lipid packing defects were not sufficient to promote their recruitment to synthetic vesicles; suggesting that RAB4 and RAB11 require more demanding membrane physicochemical properties. Our work demonstrates that the properties of membranes are critical for the regulation of RAB specific membrane targeting.
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https://tel.archives-ouvertes.fr/tel-01816178
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Submitted on : Friday, June 15, 2018 - 1:02:52 AM
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  • HAL Id : tel-01816178, version 1

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Guillaume Kulakowski. Membrane binding properties of RAB GTPases. Biophysics. Université Pierre et Marie Curie - Paris VI, 2017. English. ⟨NNT : 2017PA066358⟩. ⟨tel-01816178⟩

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