The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms (Journal article)

Schnatwinkel, C./ Christoforidis, S./ Lindsay, M. R./ Uttenweiler-Joseph, S./ Wilm, M./ Parton, R. G./ Zerial, M.


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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adenoviridae/genetics,Androstadienes/pharmacology,Animals,Cell Line,Cell Line, Tumor,Cell Membrane/metabolism,Cloning, Molecular,Dogs,Down-Regulation,Endocytosis/*physiology,Endosomes/metabolism,Enzyme Inhibitors/pharmacology,Epithelial Cells/cytology,Fibroblasts/metabolism,GTP Phosphohydrolases/chemistry,*Gene Expression Regulation,Humans,Inositol Phosphates/chemistry,Intracellular Signaling Peptides and Proteins/genetics/*physiology,Liposomes/metabolism,Mice,Microscopy, Confocal,Microscopy, Video,Movement,NIH 3T3 Cells,Pinocytosis,Plasmids/metabolism,Protein Binding,Protein Structure, Tertiary,RNA Interference,Recombinant Proteins/chemistry,Time Factors,rab5 GTP-Binding Proteins/*physiology
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/23499
ISSN: 1545-7885
Link: http://www.ncbi.nlm.nih.gov/pubmed/15328530
http://www.plosbiology.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pbio.0020261&representation=PDF
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