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  The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms.

Schnatwinkel, C., Christoforidis, S., Lindsay, M. R., Uttenweiler-Joseph, S., Wilm, M., Parton, R. G., et al. (2004). The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms. PLoS Biology, 2(9).

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Schnatwinkel, Carsten1, Author           
Christoforidis, Savvas, Author
Lindsay, Margaret R, Author
Uttenweiler-Joseph, Sandrine, Author
Wilm, Matthias, Author
Parton, Robert G, Author
Zerial, Marino1, Author           
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: 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: 2004
 Publication Status: Issued
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 Identifiers: eDoc: 229783
Other: 484
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Title: PLoS Biology
Source Genre: Journal
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Pages: - Volume / Issue: 2 (9) Sequence Number: - Start / End Page: - Identifier: -