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          Institute: MPI für experimentelle Medizin     Collection: Molecular Neurobiology     Display Documents



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ID: 292165.0, MPI für experimentelle Medizin / Molecular Neurobiology
Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2
Authors:Andrews-Zwilling, Yaisa S.; Kawabe, Hiroshi; Reim, Kerstin; Varoqueaux, Frédérique; Brose, Nils
Language:English
Date of Publication (YYYY-MM-DD):2006-07
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J.Biol. Chem.
Volume:281
Issue / Number:28
Start Page:19720
End Page:19731
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Transmitter release at synapses between nerve cells is spatially restricted to active zones, where synaptic vesicle docking, priming, and Ca2+-dependent fusion take place in a temporally highly coordinated manner. Munc13s are essential for priming synaptic vesicles to a fusion competent state, and their specific active zone localization contributes to the active zone restriction of transmitter release and the speed of excitation-secretion coupling. However, the molecular mechanism of the active zone recruitment of Munc13s is not known. We show here that the active zone recruitment of Munc13 isoforms Munc13-1 and ubMunc13-2 is regulated by their binding to the Rab3A-interacting molecule RIM1 alpha, a key determinant of long term potentiation of synaptic transmission at mossy fiber synapses in the hippocampus. We identify a single point mutation in Munc13-1 and ubMunc13-2 (I121N) that, depending on the type of assay used, strongly perturbs or abolishes RIM1 alpha binding in vitro and in cultured fibroblasts, and we demonstrate that RIM1 alpha binding-deficient ubMunc13-2(I121) is not efficiently recruited to synapses. Moreover, the levels of Munc13-1 and ubMunc13-2 levels are decreased in RIM1 alpha-deficient brain, and Munc13-1 is not properly enriched at active zones of mossy fiber terminals of the mouse hippocampus if RIM1 alpha is absent. We conclude that one function of the Munc13/RIM1 alpha interaction is the active zone recruitment of Munc13-1 and ubMunc13-2.
Free Keywords:LONG-TERM POTENTIATION; SYNAPTIC-VESICLE FUSION; ZONE PROTEIN RIM1-ALPHA; ACTIVE-ZONE; NEUROTRANSMITTER RELEASE; FUNCTIONAL INTERACTION; TRANSMITTER RELEASE; CHROMAFFIN CELLS; UNC-13; FAMILY
External Publication Status:published
Document Type:Article
Communicated by:Nils Brose
Affiliations:MPI für experimentelle Medizin/Molecular neurobiology
Identifiers:ISSN:0021-9258 [ID No:1]
ISI:000238847000085 [ID No:2]
ISI:000238847000085 [ID No:3]
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