Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming

Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca 2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 2001-04, Vol.30 (1), p.183-196
Hauptverfasser: Betz, Andrea, Thakur, Pratima, Junge, Harald J., Ashery, Uri, Rhee, Jeong-Seop, Scheuss, Volker, Rosenmund, Christian, Rettig, Jens, Brose, Nils
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container_end_page 196
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container_title Neuron (Cambridge, Mass.)
container_volume 30
creator Betz, Andrea
Thakur, Pratima
Junge, Harald J.
Ashery, Uri
Rhee, Jeong-Seop
Scheuss, Volker
Rosenmund, Christian
Rettig, Jens
Brose, Nils
description Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca 2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
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subjects Alternative Splicing - genetics
Animals
Binding Sites - genetics
Cells, Cultured
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Fungal Proteins - genetics
Fungal Proteins - metabolism
Molecular Sequence Data
Munc13-1 protein
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons - metabolism
Neurotransmitter Agents - metabolism
Presynaptic Terminals - metabolism
Protein Isoforms - genetics
Protein Isoforms - metabolism
Protein Structure, Tertiary - genetics
rab3A GTP-Binding Protein - metabolism
RIM1 protein
Sequence Homology, Amino Acid
Synaptic Transmission - physiology
Synaptic Vesicles - metabolism
Two-Hybrid System Techniques
Zinc Fingers - physiology
title Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming
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