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

Cell. 1994 Nov 18;79(4):717-27. doi: 10.1016/0092-8674(94)90556-8.

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 Ca(2+)-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 alpha-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 Ca(2+)-independent release. We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Brain / physiology*
  • Calcium / metabolism*
  • Calcium-Binding Proteins*
  • DNA Primers
  • Exons
  • Hippocampus / physiology*
  • Homozygote
  • Hypertonic Solutions
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / metabolism*
  • Polymerase Chain Reaction
  • Reference Values
  • Restriction Mapping
  • Spider Venoms / pharmacology
  • Synapses / drug effects
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptotagmin I
  • Synaptotagmins

Substances

  • Calcium-Binding Proteins
  • DNA Primers
  • Hypertonic Solutions
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Spider Venoms
  • Synaptotagmin I
  • Syt1 protein, mouse
  • Synaptotagmins
  • alpha-latrotoxin
  • Calcium