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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Calcium / metabolism*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Calcium-Binding Proteins / physiology*
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Cells, Cultured
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism
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Neurotransmitter Agents / chemistry
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Neurotransmitter Agents / genetics
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Neurotransmitter Agents / metabolism
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Neurotransmitter Agents / physiology*
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Point Mutation
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Protein Binding
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Protein Conformation
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Synapses / physiology*
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Synaptic Vesicles / metabolism
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Synaptotagmin I
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Synaptotagmins
Substances
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Calcium-Binding Proteins
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Synaptotagmin I
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Syt1 protein, mouse
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Synaptotagmins
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Calcium