Synaptotagmin mutants Y311N and K326/327A alter the calcium dependence of neurotransmission

Catherine R. Borden, Charles F. Stevens, Jane M. Sullivan*, Yongling Zhu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Synaptotagmin I, a calcium-binding synaptic vesicle protein, is thought to act as the calcium sensor for fast neurotransmission, but what synaptotagmin I does, upon binding calcium, to trigger exocytosis is still unknown. To begin to examine the role of synaptotagmin I's interactions with calcium-dependent binding partners, three mutant versions of synaptotagmin I reported to affect calcium-dependent self-oligomerization (Y311N, K327A, and K326/327A) were expressed in cultured mouse hippocampal neurons lacking endogenous synaptotagmin I, and effects on neurotransmission were evaluated by comparison with transmission rescued by wild-type synaptotagmin I. All three mutants reduced transmitter release. To separate effects on calcium binding from effects on calcium-dependent oligomerization, we measured the calcium dependence of exocytosis for two of the mutants. Both showed apparent calcium affinity much lower than wild-type, a reduction sufficient to account for the neurotransmission defects. We conclude that self-oligomerization is unlikely to play any significant role in triggering synaptic vesicle exocytosis.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume29
Issue number3
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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