N-type voltage-sensitive calcium channel interacts with syntaxin, synaptotagmin and SNAP-25 in a multiprotein complex

Dror Tobi, Ofer Wiser, Michael Trus, Daphne Atlas

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Expression of the N-type voltage sensitive calcium channel in Xenopus oocytes along with syntaxin and p65 showed that the syntaxin-modified N-type channel properties, were fully reversed by p65. The inward current was restored to a significantly higher amplitude when all three proteins were present, suggesting that the channel interacts with syntaxin, p65 and SNAP-25 in a quaternary complex. Further support to a multicomplex formation between the channel and the synaptic proteins was drawn from the steady-state voltage inactivation profiles. A physical interaction of the N-type calcium channel with the vesicular protein synaptotagmin (p65) was demonstrated biochemically, using recombinant fusion proteins. The interaction is confined to a cytosolic channel domain that separates segments II and III amino acids 710-1090 of the N-type channel (N-Loop710-1090. In vitro binding of recombinant N-Loop710-1090 to p65 (amino acids 96-421) involves the two C2 domains of p65, C2A domain [amino acids 96-265; p65(1-3)] and C2B domain [amino acids 248-421; p65(3-5)]. While the binding of C2A and C2B domains was calcium independent, C2B domain binding to the N-Loop was inositol-hexaphosphate (IP6)-sensitive. The N-Loop710-1090 binding to p65 was competed by syntaxin and SNAP-25, which are synaptic plasma membrane proteins. These combined functional and biochemical approaches provide evidence for a complex formation between the N-type channel and the exocytotic machinery which by generating fusion-competent vesicles may function to regulate the process of synaptic secretion.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalReceptors and Channels
Issue number2
StatePublished - 1998
Externally publishedYes


  • Exocytosis
  • N-type calcium channel
  • SNAP-25
  • Secretion
  • Synaptotagmin
  • Syntaxin


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