BRITTAIN, J. M.PIEKARZ, A. D.PIEKARZ, Y. WANGGARCIA, A. S.CUMMINS, T. R.KHANNA, R.2016-10-272016-10-272010-04-09J. M., BRITTAIN, A. D. PIEKARZ, Y., WANG, A. S. GARCIA, T. R., CUMMINS, R. KHANNA. (2010, April 9). An atypical role for CRMP-2 in neurotransmitter release via interaction with presynaptic Ca2+ channels. Poster session presented at IUPUI Research Day 2010, Indianapolis, Indiana.https://hdl.handle.net/1805/11261poster abstractCollapsin 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 Ca2+ channel (CaV2.2) as a CRMP-2interacting protein. CRMP-2 binds directly to CaV2.2 in two regions; the channel domain I-II intracellular loop and the distal C-terminus, but not to any other regions. Both proteins colocalize within presynaptic sites in hippocampal neurons. Overexpression in hippocampal neurons of a CRMP-2 protein fused to EGFP caused a significant increase in Ca2+ channel current density whereas lentivirus-mediated CRMP-2 knockdown abolished this effect. Interestingly, the increase in Ca2+ 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-EGFP overexpressing neurons elicited a significant increase in release of glutamate compared to control neurons. Toxin block of Ca2+ entry via CaV2.2 abolished this stimulated release. Thus, the CRMP-2-Ca2+ channel interaction represents a novel mechanism for modulation of Ca2+ influx into nerve terminals and, hence, of synaptic strength.en-USCollapsin response mediator proteins (CRMPs)neuronsprotein-protein interactionspresynaptic Ca2+ channelsPoster