Titre
Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Coppola, T.
Auteure/Auteur
Perret-Menoud, V.
Auteure/Auteur
Luthi, S.
Auteure/Auteur
Farnsworth, C. C.
Auteure/Auteur
Glomset, J. A.
Auteure/Auteur
Regazzi, R.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0261-4189
Statut éditorial
Publié
Date de publication
1999-11
Volume
18
Numéro
21
Première page
5885
Dernière page/numéro d’article
91
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 1
Research Support, Non-U.S. Gov't --- Old month value: Nov 1
Résumé
Rab GTPases regulate membrane traffic between the cellular compartments of eukaryotic cells. Rab3 is associated with secretory vesicles of neuronal and endocrine cells and controls the Ca(2+)-triggered release of neurotransmitters and hormones. To clarify the mode of action of Rab3 we generated mutants of the GTPase that do not interact efficiently with its putative effectors Rabphilin and RIM. Surprisingly, these mutants transfected in PC12 cells were still capable of inhibiting Ca(2+)-evoked secretion. Rab3 was shown previously to bind to calmodulin in a Ca(2+)-dependent manner. By replacing two arginines conserved between Rab3 isoforms, we generated a mutant with a reduced affinity for calmodulin. This mutant retained the capacity to interact with the Rab3 regulatory proteins, Rabphilin, RIM, Mss4 and RabGDI, and was correctly targeted to dense-core secretory granules. However, replacement of the two arginines abolished the ability of the GTP-bound form of Rab3 to inhibit exocytosis of catecholamine- and insulin-secreting cells. We propose that a Rab3-calmodulin complex generated by elevated Ca(2+) concentrations mediated at least some of the effects of the GTPase and limited the number of exocytotic events that occurred in response to secretory stimuli.
Sujets
PID Serval
serval:BIB_409E0C7774EB
PMID
Open Access
Oui
Date de création
2008-01-24T13:30:11.024Z
Date de création dans IRIS
2025-05-20T18:51:24Z