RGD Reference Report - Rab3-interacting molecule gamma isoforms lacking the Rab3-binding domain induce long lasting currents but block neurotransmitter vesicle anchoring in voltage-dependent P/Q-type Ca2+ channels. - Rat Genome Database

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Rab3-interacting molecule gamma isoforms lacking the Rab3-binding domain induce long lasting currents but block neurotransmitter vesicle anchoring in voltage-dependent P/Q-type Ca2+ channels.

Authors: Uriu, Y  Kiyonaka, S  Miki, T  Yagi, M  Akiyama, S  Mori, E  Nakao, A  Beedle, AM  Campbell, KP  Wakamori, M  Mori, Y 
Citation: Uriu Y, etal., J Biol Chem. 2010 Jul 9;285(28):21750-67. doi: 10.1074/jbc.M110.101311. Epub 2010 May 7.
RGD ID: 8554325
Pubmed: PMID:20452978   (View Abstract at PubMed)
PMCID: PMC2898395   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.101311   (Journal Full-text)

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 beta-subunits physically interact with the long alpha isoform of the presynaptic active zone scaffolding protein RIM1 (RIM1alpha) via its C terminus containing the C(2)B domain. This interaction cooperates with RIM1alpha-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 gamma isoforms (gamma-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 alpha-RIMs, including RIM1alpha. Here, we demonstrate that gamma-RIMs also exert prominent suppression of VDCC inactivation via direct binding to beta-subunits. In the pheochromocytoma PC12 cells, this common functional feature allows native RIMs to enhance acetylcholine secretion, whereas gamma-RIMs are uniquely different from alpha-RIMs in blocking localization of neurotransmitter-containing vesicles near the plasma membrane. Gamma-RIMs as well as alpha-RIMs show wide distribution in central neurons, but knockdown of gamma-RIMs attenuated glutamate release to a lesser extent than that of alpha-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 alpha-RIMs with gamma-RIMs for VDCC beta-subunits.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of synaptic vesicle exocytosis acts_upstream_of_or_withinIMP 8554325; 8554325PMID:20452978MGI 

Objects Annotated

Genes (Rattus norvegicus)
Rims3  (regulating synaptic membrane exocytosis 3)
Rims4  (regulating synaptic membrane exocytosis 4)


Additional Information