RIM1α 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

Research output: Contribution to journalArticlepeer-review

493 Scopus citations

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 RIM1α, 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 α-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1α in mice shows that RIM1α is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1α has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalNature
Volume415
Issue number6869
DOIs
StatePublished - Jan 17 2002

ASJC Scopus subject areas

  • General

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