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Interactions of Presynaptic Ca 2+ Channels and Snare Proteins in Neurotransmitter Release
Author(s) -
CATTERALL WILLIAM A.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11284.x
Subject(s) - syntaxin , exocytosis , synaptotagmin 1 , synaptic vesicle , chemistry , stx1a , microbiology and biotechnology , neurotransmitter , neurotransmission , biophysics , vesicle , biology , secretion , biochemistry , receptor , membrane
N‐ and P/Q‐type Ca 2+ channels are localized in high density in presynaptic nerve terminals and are crucial elements in neuronal excitation‐secretion coupling. In addition to mediating Ca 2+ entry to initiate transmitter release, they are thought to interact directly with proteins of the synaptic vesicle docking/fusion machinery. These Ca 2+ channels can be purified from brain as a complex with SNARE proteins, which are involved in exocytosis. In addition, N‐type and P/Q‐type Ca 2+ channels are colocalized with syntaxin in high‐density clusters in nerve terminals. The synaptic protein interaction (synprint) sites in the intracellular loop II‐III (L II‐III ) of both α 1B and α 1A subunits of N‐type and P/Q‐type Ca 2+ channels bind to syntaxin, SNAP‐25, and synaptotagmin.Ca 2+ has a biphasic effect on the interactions of N‐type Ca 2+ channels with SNARE complexes, stimulating optimal binding in the range of 10–30 μM. PKC or CaM KII phosphorylation of the N‐type synprint peptide inhibits interactions with SNARE complexes containing syntaxin and SNAP‐25. Introduction of the synprint peptides into presynaptic superior cervical ganglion neurons reversibly inhibits EPSPs from synchronous transmitter release by 42%. At physiological Ca 2+ concentrations, synprint peptides significantly reduce transmitter release in injected frog neuromuscular junctions in cell culture, consistent with detachment of 70% of the docked vesicles from Ca 2+ channels as analyzed by a theoretical model. Together, these studies suggest that presynaptic Ca 2+ channels not only provide the Ca 2+ signal required by the exocytotic mechinery, but also contain structural elements that are integral to vesicle docking, priming, and fusion processes.