Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

Yoshitsugu Uriu; Shigeki Kiyonaka; Takafumi Miki; Masakuni Yagi; Satoshi Akiyama; Emiko Mori; Akito Nakao; Aaron M Beedle; Kevin P Campbell; Minoru Wakamori; Yasuo Mori

doi:10.1074/jbc.M110.101311

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Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

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Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

Yoshitsugu Uriu, Shigeki Kiyonaka, Takafumi Miki, Masakuni Yagi, Satoshi Akiyama, Emiko Mori, Akito Nakao, Aaron M Beedle, Kevin P Campbell, Minoru Wakamori, …

The Journal of biological chemistry, Vol.285(28), pp.21750-21767

07/09/2010

DOI: 10.1074/jbc.M110.101311

PMCID: PMC2898395

PMID: 20452978

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Abstract

Assembly of voltage-dependent Ca 2+ channels (VDCCs) with their associated proteins regulates the coupling of VDCCs with upstream and downstream cellular events. Among the four isoforms of the Rab3-interacting molecule (RIM1 to -4), we have previously reported that VDCC β-subunits physically interact with the long α isoform of the presynaptic active zone scaffolding protein RIM1 (RIM1α) via its C terminus containing the C 2 B domain. This interaction cooperates with RIM1α-Rab3 interaction to support neurotransmitter exocytosis by anchoring vesicles in the vicinity of VDCCs and by maintaining depolarization-triggered Ca 2+ influx as a result of marked inhibition of voltage-dependent inactivation of VDCCs. However, physiological functions have not yet been elucidated for RIM3 and RIM4, which exist only as short γ isoforms (γ-RIMs), carrying the C-terminal C 2 B domain common to RIMs but not the Rab3-binding region and other structural motifs present in the α-RIMs, including RIM1α. Here, we demonstrate that γ-RIMs also exert prominent suppression of VDCC inactivation via direct binding to β-subunits. In the pheochromocytoma PC12 cells, this common functional feature allows native RIMs to enhance acetylcholine secretion, whereas γ-RIMs are uniquely different from α-RIMs in blocking localization of neurotransmitter-containing vesicles near the plasma membrane. γ-RIMs as well as α-RIMs show wide distribution in central neurons, but knockdown of γ-RIMs attenuated glutamate release to a lesser extent than that of α-RIMs in cultured cerebellar neurons. The results suggest that sustained Ca 2+ influx through suppression of VDCC inactivation by RIMs is a ubiquitous property of neurons, whereas the extent of vesicle anchoring to VDCCs at the plasma membrane may depend on the competition of α-RIMs with γ-RIMs for VDCC β-subunits.

Neurotransmitters

Vesicles

Calcium Channels

Voltage-dependent Inactivation

Membrane Biology

Neurobiology

Exocytosis

Rab3-interacting Molecule

Voltage-dependent Calcium Channel Beta Subunit

Protein Assembly

Details

Title: Subtitle: Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels
Creators: Yoshitsugu Uriu - From the
Shigeki Kiyonaka - From the
Takafumi Miki - From the
Masakuni Yagi - From the
Satoshi Akiyama - From the
Emiko Mori - From the
Akito Nakao - From the
Aaron M Beedle - the
Kevin P Campbell - the
Minoru Wakamori - the
Yasuo Mori - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.285(28), pp.21750-21767
DOI: 10.1074/jbc.M110.101311
PMID: 20452978
PMCID: PMC2898395
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Language: English
Date published: 07/09/2010
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984014000202771

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