title: Identification of a syntaxin-binding site on N-type calcium channels.
abstract: Immunochemical studies have suggested a tight association of syntaxin with N-type calcium channels. Syntaxin specifically interacts with the fusion proteins containing the cytoplasmic loop (LII-III) between homologous repeats II and III of the alpha 1 subunit of the class B N-type calcium channel (alpha 1B) from rat brain, but not with those of the class A Q-type (alpha 1A) or the class S L-type (alpha 1S) calcium channels. This interaction is mediated by an 87 amino acid sequence (773-859) containing two overlapping predicted helix-loop-helix domains. The 87 amino acid peptide can specifically block binding of native N-type calcium channels to syntaxin, indicating that this binding site is required for stable interaction of these two proteins. Interaction takes place with the C-terminal one-third of syntaxin (residues 181-288), which is thought to be anchored in the presynaptic plasma membrane. Our results suggest a direct interaction between the cytoplasmic domains of these two presynaptic membrane proteins that could have an important role in the targeting and docking of synaptic vesicles near N-type calcium channels, enabling tight structural and functional association of calcium entry sites and neurotransmitter release sites.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle 98195.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Sheng
authors.forename: J
authors.initials: J
authors.lastname: Rettig
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000648:ultrastructure; D015220:Calcium Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D050765:Qa-SNARE Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D020866:omega-Conotoxin GVIA
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D010455:Peptides; D050765:Qa-SNARE Proteins; D020866:omega-Conotoxin GVIA