RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone

Susanne Schoch; Pablo E Castillo; Tobias Jo; Konark Mukherjee; Martin Geppert; Yun Wang; Frank Schmitz; Robert C Malenka; Thomas C Südhof

doi:10.1038/415321a

RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone

Nature. 2002 Jan 17;415(6869):321-6. doi: 10.1038/415321a.

Authors

Susanne Schoch¹, Pablo E Castillo, Tobias Jo, Konark Mukherjee, Martin Geppert, Yun Wang, Frank Schmitz, Robert C Malenka, Thomas C Südhof

Affiliation

¹ The Center for Basic Neuroscience and Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.

PMID: 11797009
DOI: 10.1038/415321a

Abstract

Neurotransmitters are released by synaptic vesicle fusion at the active zone. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood. Here we show that RIM1alpha, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1alpha in mice shows that RIM1alpha is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Brain / metabolism
COS Cells
Dizocilpine Maleate
GTP-Binding Proteins*
In Vitro Techniques
Intracellular Signaling Peptides and Proteins
Macromolecular Substances
Mice
Mice, Knockout
Mutation
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Nerve Tissue Proteins / physiology*
Neuronal Plasticity
Neurotransmitter Agents / metabolism*
Phosphoproteins / metabolism
Phosphoproteins / physiology
Presynaptic Terminals / metabolism
Presynaptic Terminals / physiology*
Protein Binding
Protein Isoforms / genetics
rab3A GTP-Binding Protein / metabolism

Substances

Adaptor Proteins, Signal Transducing
Intracellular Signaling Peptides and Proteins
Macromolecular Substances
Nerve Tissue Proteins
Neurotransmitter Agents
Phosphoproteins
Ppfia4 protein, rat
Protein Isoforms
RIMS1 protein, human
Rim protein, mammalian
Rims1 protein, mouse
Rims1 protein, rat
UNC13B protein, human
Unc13b protein, mouse
Unc13c protein, mouse
Dizocilpine Maleate
GTP-Binding Proteins
rab3A GTP-Binding Protein