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.
Pubmed ID: 11242035 RIS Download
Mesh terms: Animals | Calcium | Calcium-Binding Proteins | Cells, Cultured | Membrane Glycoproteins | Mice | Mutagenesis, Site-Directed | Nerve Tissue Proteins | Neurons | Neurotransmitter Agents | Point Mutation | Protein Binding | Protein Conformation | Synapses | Synaptic Vesicles | Synaptotagmin I | Synaptotagmins
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