Cell
Volume 79, Issue 4, 18 November 1994, Pages 717-727
Journal home page for Cell

Article
Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse

https://doi.org/10.1016/0092-8674(94)90556-8Get rights and content

Abstract

Mice carrying a mutation in the synaptotagmin I gene were generated by homologous recombination. Mutant mice are phenotypically normal as heterozygotes, but die within 48 hr after birth as homozygotes. Studies of hippocampal neurons cultured from homozygous mutant mice reveal that synaptic transmission is severely impaired. The synchronous, fast component of Ca2+-dependent neurotransmitter release is decreased, whereas asynchronous release processes, including spontaneous synaptic activity (miniature excitatory postsynaptic current frequency) and release triggered by hypertonic solution or α-latrotoxin, are unaffected. Our findings demonstrate that synaptotagmin I function is required for Ca2+-triggering of synchronous neurotransmitter release, but is not essential for asynchronous or Ca2+-independent release. We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons.

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