A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant synapse

T. Dresbach, Marie E Burns, V. O'Connor, W. M. DeBello, H. Betz, G. J. Augustine

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Sec1-related proteins are essential for membrane fusion at distinct stages of the constitutive and regulated secretory pathways in eukaryotic cells. Studies of neuronal isoforms of the Sec1 protein family have yielded evidence for both positive and negative regulatory functions of these proteins in neurotransmitter release. Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and examined its function in neurotransmitter release at the squid giant synapse. Microinjection of s- Sec1 into the presynaptic terminal of the giant synapse inhibited evoked neurotransmitter release, but this effect was prevented by coinjecting the cytoplasmic domain of squid syntaxin (s-syntaxin), one of the binding partners of s-Sec1. A 24 amino acid peptide fragment of s-Sec1, which inhibited the binding of s-Sec1 to s-syntaxin in vitro, completely blocked release, suggesting an essential function of the s-Sec1/s-syntaxin interaction in transmitter release. Electron microscopy showed that injection of s-Sec1 did not change the spatial distribution of synaptic vesicles at presynaptic release sites ('active zones'), whereas the inhibitory peptide increased the number of docked vesicles. These distinct morphological effects lead us to conclude that Sec1 proteins function at different stages of synaptic vesicle exocytosis, and that an interaction of s-Sec1 with syntaxin - at a stage blocked by the peptide - is necessary for docked vesicles to fuse.

Original languageEnglish (US)
Pages (from-to)2923-2932
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number8
StatePublished - Apr 15 1998
Externally publishedYes

    Fingerprint

Keywords

  • Active zone
  • Microinjection
  • Neurotransmitter release
  • Sec1 proteins
  • Squid giant synapse
  • Syntaxin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dresbach, T., Burns, M. E., O'Connor, V., DeBello, W. M., Betz, H., & Augustine, G. J. (1998). A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant synapse. Journal of Neuroscience, 18(8), 2923-2932.