Synaptotagmin I Functions as a Calcium Regulator of Release Probability

Nature. 2001 Mar 1;410(6824):41-9. doi: 10.1038/35065004.

Abstract

In all synapses, Ca2+ triggers neurotransmitter release to initiate signal transmission. Ca2+ presumably acts by activating synaptic Ca2+ sensors, but the nature of these sensors--which are the gatekeepers to neurotransmission--remains unclear. One of the candidate Ca2+ sensors in release is the synaptic Ca2+-binding protein synaptotagmin I. Here we have studied a point mutation in synaptotagmin I that causes a twofold decrease in overall Ca2+ affinity without inducing structural or conformational changes. When introduced by homologous recombination into the endogenous synaptotagmin I gene in mice, this point mutation decreases the Ca2+ sensitivity of neurotransmitter release twofold, but does not alter spontaneous release or the size of the readily releasable pool of neurotransmitters. Therefore, Ca2+ binding to synaptotagmin I participates in triggering neurotransmitter release at the synapse.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Calcium-Binding Proteins / physiology*
  • Cells, Cultured
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Neurotransmitter Agents / chemistry
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / physiology*
  • Point Mutation
  • Protein Binding
  • Protein Conformation
  • Synapses / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptotagmin I
  • Synaptotagmins

Substances

  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Synaptotagmin I
  • Syt1 protein, mouse
  • Synaptotagmins
  • Calcium