title: Calcium-dependent interaction of N-type calcium channels with the synaptic core complex.
abstract: Neurotransmitter release is initiated by influx of Ca2+ through voltage-gated Ca2+ channels, within 200 microseconds of the action potential arriving at the synaptic terminal, as the Ca2+ concentration increases from 100 nM to > 200 microM. Exocytosis requires high Ca2+ concentration, with a threshold of 20-50 microM and half-maximal activation at 190 microM. The synaptic membrane proteins syntaxin, 25K synaptosome-associated protein (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin, are thought to form a synaptic core complex which mediates vesicle docking and membrane fusion. Synaptotagmin may be the low-affinity Ca(2+)-sensor, but other Ca(2+)-sensors are involved as residual neurotransmission persists in synaptotagmin-null mutants. Syntaxin binds to N-type Ca2+ channels at a site in the intracellular loop connecting domains II and III. Here we describe Ca(2+)-dependent interaction of this site with syntaxin and SNAP25 which has a biphasic dependence on Ca2+, with maximal binding at 20 microM free Ca2+, near the threshold for transmitter release. Ca(2+)-dependent interaction of Ca2+ channels with the synaptic core complex may be important for Ca(2+)-dependent docking and fusion of synaptic vesicles.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle 98195-7280, USA.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Sheng
authors.forename: J
authors.initials: J
authors.lastname: Rettig
authors.forename: T
authors.initials: T
authors.lastname: Cook
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050765:Qa-SNARE Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D050857:Synaptotagmins
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050857:Synaptotagmins; D002118:Calcium