Genetic analysis of synaptotagmin 2 in spontaneous and Ca 2+-triggered neurotransmitter release

Zhiping P. Pang, Jianyuan Sun, Jose Rizo-Rey, Anton Maximov, Thomas C. Südhof

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca2+-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca2+ triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca2+ triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling 'release slots' for synaptic vesicles at the active zone.

Original languageEnglish (US)
Pages (from-to)2039-2050
Number of pages12
JournalEMBO Journal
Volume25
Issue number10
DOIs
StatePublished - May 17 2006

Keywords

  • Calyx of Held
  • Neuromuscular junctions
  • Synaptic transmission
  • Synaptotagmin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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