Abstract
NEUROTRANSMITTER release is initiated by influx of Ca2+ through voltage-gated Ca2+ channels1,2, within 200 μs of the action potential arriving at the synaptic terminal3, as the Ca2+ concentration increases from 100 nM to >200μM4. Exocytosis requires high Ca2+ concentration, with a threshold of 20–50 μM and half-maximal activation at 190 μM5,6. The synaptic membrane proteins syntaxin7,8, 25K synaptosome-associated protein (SNAP25)9, and vesicle-associated membrane protein (VAMP)/ synaptobrevin10–12, are thought to form a synaptic core complex which mediates vesicle docking and membrane fusion13–19. Synaptotagmin may be the low-affinity Ca2+-sensor20–24, but other Ca2+-sensors are involved25–27 as residual neurotransmission persists in synaptotagmin-null mutants. Syntaxin binds to N-type Ca2+ channels7,8,28,29 at a site in the intracellular loop connecting domains II and III30. Here we describe Ca2+-dependent interaction of this site with syntaxin and SNAP25 which has a biphasic dependence on Ca2+, with maximal binding at 20 μM free Ca2+, near the threshold for transmitter release. Ca2+-dependent interaction of Ca2+ channels with the synaptic core complex may be important for Ca2+-dependent docking and fusion of synaptic vesicles.
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Sheng, ZH., Rettig, J., Cook, T. et al. Calcium-dependent interaction of N-type calcium channels with the synaptic core complex. Nature 379, 451–454 (1996). https://doi.org/10.1038/379451a0
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DOI: https://doi.org/10.1038/379451a0
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