The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms
Φόρτωση...
Ημερομηνία
Συγγραφείς
Schnatwinkel, C.
Christoforidis, S.
Lindsay, M. R.
Uttenweiler-Joseph, S.
Wilm, M.
Parton, R. G.
Zerial, M.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
PLoS Biol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
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
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
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
http://www.plosbiology.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pbio.0020261&representation=PDF
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής