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Article Dans Une Revue PLoS Biology Année : 2004

The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms

Résumé

The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells.
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Dates et versions

hal-02506227 , version 1 (12-03-2020)

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Carsten Schnatwinkel, Savvas Christoforidis, Margaret R. Lindsay, Sandrine Uttenweiler-Joseph, Matthias Wilm, et al.. The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms. PLoS Biology, 2004, 2 (9), pp.e261. ⟨10.1371/journal.pbio.0020261⟩. ⟨hal-02506227⟩
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