RGD Reference Report - An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels.

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An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels.
Authors:	Brittain, JM Piekarz, AD Wang, Y Kondo, T Cummins, TR Khanna, R
Citation:	Brittain JM, etal., J Biol Chem. 2009 Nov 6;284(45):31375-90. Epub 2009 Sep 15.
RGD ID:	2316240
Pubmed:	PMID:19755421 (View Abstract at PubMed)
PMCID:	PMC2781534 (View Article at PubMed Central)
DOI:	DOI:10.1074/jbc.M109.009951 (Journal Full-text)
Collapsin response mediator proteins (CRMPs) specify axon/dendrite fate and axonal growth of neurons through protein-protein interactions. Their functions in presynaptic biology remain unknown. Here, we identify the presynaptic N-type Ca(2+) channel (CaV2.2) as a CRMP-2-interacting protein. CRMP-2 binds directly to CaV2.2 in two regions: the channel domain I-II intracellular loop and the distal C terminus. Both proteins co-localize within presynaptic sites in hippocampal neurons. Overexpression in hippocampal neurons of a CRMP-2 protein fused to enhanced green fluorescent protein caused a significant increase in Ca(2+) channel current density, whereas lentivirus-mediated CRMP-2 knockdown abolished this effect. Interestingly, the increase in Ca(2+) current density was not due to a change in channel gating. Rather, cell surface biotinylation studies showed an increased number of CaV2.2 at the cell surface in CRMP-2-overexpressing neurons. These neurons also exhibited a significant increase in vesicular release in response to a depolarizing stimulus. Depolarization of CRMP-2-enhanced green fluorescent protein-overexpressing neurons elicited a significant increase in release of glutamate compared with control neurons. Toxin block of Ca(2+) entry via CaV2.2 abolished this stimulated release. Thus, the CRMP-2-Ca(2+) channel interaction represents a novel mechanism for modulation of Ca(2+) influx into nerve terminals and, hence, of synaptic strength.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dpysl2	Rat	positive regulation of glutamate secretion		IDA			RGD
Dpysl2	Rat	synaptic vesicle transport		IDA			RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dpysl2	Rat	dendrite		IDA			RGD
Dpysl2	Rat	presynapse	is_active_in	IDA		PMID:19755421	SynGO
Dpysl2	Rat	protein-containing complex		IDA			RGD
Dpysl2	Rat	synapse	is_active_in	IDA		PMID:19755421	SynGO
Dpysl2	Rat	synapse	is_active_in	IMP		PMID:19755421	SynGO
Dpysl2	Rat	terminal bouton	located_in	IDA			RGD

Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Cacna1b	Rat	protein binding		IPI	Dpysl2 (Rattus norvegicus)		RGD
Dpysl2	Rat	protein binding		IPI	Cacna1b (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Cacna1b (calcium voltage-gated channel subunit alpha1 B)

Dpysl2 (dihydropyrimidinase-like 2)

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An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels.