Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Rabaptin-5

Détails

ID Serval
serval:BIB_D64AD9E8854A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Rabaptin-5
Périodique
Journal of Cell Science
Auteur(s)
Coppola  T., Hirling  H., Perret-Menoud  V., Gattesco  S., Catsicas  S., Joberty  G., Macara  I. G., Regazzi  R.
ISSN
0021-9533 (Print)
Statut éditorial
Publié
Date de publication
05/2001
Volume
114
Numéro
Pt 9
Pages
1757-64
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
Rabphilin is a secretory vesicle protein that interacts with the GTP-bound form of the small GTPase Rab3. We investigated the involvement of Rabphilin in endocytosis using different point mutants of the protein. Overexpression of wild-type Rabphilin in the insulin-secreting cell line HIT-T15 did not affect receptor-mediated transferrin endocytosis. By contrast, Rabphilin V61A, a mutant that is unable to interact with Rab3, enhanced the rate of transferrin internalization. The effect of Rabphilin V61A was not mimicked by Rabphilin L83A, another mutant with impaired Rab3 binding. Careful analysis of the properties of the two mutants revealed that Rabphilin V61A and Rabphilin L83A are both targeted to secretory vesicles, have stimulatory activity on exocytosis, and bind equally well to alpha-actinin. However, Rabphilin L83A fails to interact with Rabaptin-5, an important component of the endocytotic machinery. These results indicate that Rabphilin promotes receptor-mediated endocytosis and that its action is negatively modulated by Rab3. We propose that the hydrolysis of GTP that is coupled to the exocytotic event disrupts the Rabphilin-Rab3 complex and permits the recruitment of Rabaptin-5 at the fusion site. Our data show that immediately after internalization the transferrin receptor and VAMP-2 colocalize on the same vesicular structures, suggesting that Rabphilin favors the rapid recycling of the components of the secretory vesicle.
Mots-clé
Cell Line Cell Membrane/metabolism *Endocytosis GTP-Binding Proteins/*metabolism Membrane Proteins/*metabolism Protein Binding *Vesicular Transport Proteins rab3 GTP-Binding Proteins/*metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 15:30
Dernière modification de la notice
20/08/2019 16:56
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