Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis

Details

Serval ID
serval:BIB_409E0C7774EB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis
Journal
EMBO Journal
Author(s)
Coppola  T., Perret-Menoud  V., Luthi  S., Farnsworth  C. C., Glomset  J. A., Regazzi  R.
ISSN
0261-4189 (Print)
Publication state
Published
Issued date
11/1999
Volume
18
Number
21
Pages
5885-91
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 1
Abstract
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.
Keywords
Adaptor Proteins, Signal Transducing Animals Calcium/pharmacology Calmodulin/*metabolism Cytoplasmic Granules/metabolism Exocytosis/*genetics GTP-Binding Proteins/metabolism Guanine Nucleotide Dissociation Inhibitors/metabolism *Guanine Nucleotide Exchange Factors Microscopy, Fluorescence Mutation Nerve Tissue Proteins/metabolism PC12 Cells Protein Binding/genetics Proteins/metabolism Rats Transfection Vesicular Transport Proteins rab GTP-Binding Proteins/metabolism rab3 GTP-Binding Proteins/genetics/*metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:30
Last modification date
20/08/2019 14:39
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