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Comments on Edward Yeh et al. (2007) International Worm Meeting "A novel putative calcium channel NCA-1 and its scaffold UNC-80 regulate synaptic activity." (0)
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Edward YEH, Sharon Ng, Mi Zhang, Ying Wang, Katya Melnik-Martinez, Kim Schuske, William Schafer, & Mei ZHEN (2007). A novel putative calcium channel NCA-1 and its scaffold UNC-80 regulate synaptic activity presented in International Worm Meeting. Unpublished information; cite only with author permission.
The entry of calcium (Ca2+) into cells is conducted through multiple Ca2+ channels that differ in composition, property and modulation. Influx of Ca2+ at synapses, typically through N-, P- and Q-type voltage-gated Ca2+ channels, is a prerequisite for vesicle fusion mediated synaptic transmission. In a screen to identify genes involved in synapse development and function, we isolated the novel putative Ca2+ channel-like protein NCA-1/UNC-77 and its accessory or scaffold protein UNC-80. Gain-of-function alleles of nca-1 lead to an abnormal distribution of an active zone marker at GABAergic synapses, constitutively activated Ca2+ influx at serotonergic synapses and hyperactivated locomotions. While nca-1 loss-of-function mutants exhibit wild type behavior, double mutants of nca-1 and nca-2 (a closely related homolog) display reduced Ca2+ influx frequency at synapses and unsustainable normal locomotion upon stimulation (fainter behavior). NCA-1 is expressed in the nervous system and is required in neurons to regulate synapse morphology and function. Unlike N/P/Q-type Ca2+ channels that closely associate with active zones, NCA-1 protein localizes to perisynaptic regions. The presence of NCA-1 perisynaptically regions requires UNC-80, a novel protein that also localizes to perisynaptic regions. Our studies thus reveal the regulation and function of a novel perisynaptic channel that determines the activation of synapses.
Authors: Edward YEH, Sharon Ng, Mi Zhang, Ying Wang, Katya Melnik-Martinez, Kim Schuske, William Schafer, Mei ZHEN