The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms.
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.
Mesh Terms:
Adenoviridae, Androstadienes, Animals, Cell Line, Cell Line, Tumor, Cell Membrane, Cloning, Molecular, Dogs, Down-Regulation, Endocytosis, Endosomes, Enzyme Inhibitors, Epithelial Cells, Fibroblasts, GTP Phosphohydrolases, Gene Expression Regulation, Humans, Inositol Phosphates, Intracellular Signaling Peptides and Proteins, Liposomes, Mice, Microscopy, Confocal, Microscopy, Video, Movement, NIH 3T3 Cells, Pinocytosis, Plasmids, Protein Binding, Protein Structure, Tertiary, RNA Interference, Recombinant Proteins, Time Factors, rab5 GTP-Binding Proteins
Adenoviridae, Androstadienes, Animals, Cell Line, Cell Line, Tumor, Cell Membrane, Cloning, Molecular, Dogs, Down-Regulation, Endocytosis, Endosomes, Enzyme Inhibitors, Epithelial Cells, Fibroblasts, GTP Phosphohydrolases, Gene Expression Regulation, Humans, Inositol Phosphates, Intracellular Signaling Peptides and Proteins, Liposomes, Mice, Microscopy, Confocal, Microscopy, Video, Movement, NIH 3T3 Cells, Pinocytosis, Plasmids, Protein Binding, Protein Structure, Tertiary, RNA Interference, Recombinant Proteins, Time Factors, rab5 GTP-Binding Proteins
PLoS Biol.
Date: Sep. 01, 2004
PubMed ID: 15328530
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