RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels

Shigeki Kiyonaka; Minoru Wakamori; Takafumi Miki; Yoshitsugu Uriu; Mio Nonaka; Haruhiko Bito; Aaron Beedle; Emiko Mori; Yuji Hara; Michel De Waard; Motoi Kanagawa; Makoto Itakura; Masami Takahashi; Kevin Campbell; Yasuo Mori

doi:10.1038/nn1904

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RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels

Journal article

Peer reviewed

RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels

Shigeki Kiyonaka, Minoru Wakamori, Takafumi Miki, Yoshitsugu Uriu, Mio Nonaka, Haruhiko Bito, Aaron Beedle, Emiko Mori, Yuji Hara, Michel De Waard, …

Nature neuroscience, Vol.10(6), pp.691-701

06/2007

DOI: 10.1038/nn1904

PMCID: PMC2687938

PMID: 17496890

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Abstract

The molecular organization of presynaptic active zones is important for the neurotransmitter release that is triggered by depolarization-induced Ca2+ influx. Here, we demonstrate a previously unknown interaction between two components of the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs), that controls neurotransmitter release in mammalian neurons. RIM1 associated with VDCC beta-subunits via its C terminus to markedly suppress voltage-dependent inactivation among different neuronal VDCCs. Consistently, in pheochromocytoma neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by the full-length and C-terminal RIM1 constructs, but membrane docking of vesicles was enhanced only by the full-length RIM1. The beta construct beta-AID dominant negative, which disrupts the RIM1-beta association, accelerated the inactivation of native VDCC currents, suppressed vesicle docking and acetylcholine release in PC12 cells, and inhibited glutamate release in cultured cerebellar neurons. Thus, RIM1 association with beta in the presynaptic active zone supports release via two distinct mechanisms: sustaining Ca2+ influx through inhibition of channel inactivation, and anchoring neurotransmitter-containing vesicles in the vicinity of VDCCs.

Brain

Synaptic Transmission

Life Sciences

Transfection

Neurons

Protein Subunits

Rats, Wistar

Calcium

Humans

Neurons and Cognition

Presynaptic Terminals

Voltage-Dependent Anion Channels

Animals, Newborn

Cells, Cultured

Gene Expression Regulation

Rats

Models, Molecular

Nerve Tissue Proteins

Neurotransmitter Agents

Two-Hybrid System Techniques

Synaptic Vesicles

Animals

Qa-SNARE Proteins

Mice

GTP-Binding Proteins

Details

Title: Subtitle: RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels
Creators: Shigeki Kiyonaka - Department of Synthetic Chemistry and Biological Chemistry
Minoru Wakamori - Department of Synthetic Chemistry and Biological Chemistry
Takafumi Miki - Department of Synthetic Chemistry and Biological Chemistry
Yoshitsugu Uriu - Department of Synthetic Chemistry and Biological Chemistry
Mio Nonaka - Department of Neurochemistry
Haruhiko Bito - Department of Neurochemistry
Aaron Beedle - Departments of Physiology and Biophysics, Internal Medicine, and Neurology
Emiko Mori - Department of Synthetic Chemistry and Biological Chemistry
Yuji Hara - Department of Synthetic Chemistry and Biological Chemistry
Michel De Waard - Canaux calciques , fonctions et pathologies
Motoi Kanagawa - Departments of Physiology and Biophysics, Internal Medicine, and Neurology
Makoto Itakura - Department of Biochemistry
Masami Takahashi - Department of Biochemistry
Kevin Campbell - Departments of Physiology and Biophysics, Internal Medicine, and Neurology
Yasuo Mori - Department of Synthetic Chemistry and Biological Chemistry
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.10(6), pp.691-701
DOI: 10.1038/nn1904
PMID: 17496890
PMCID: PMC2687938
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Publisher: Nature Publishing Group
Language: English
Date published: 06/2007
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020889402771

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