Abstract
Neurons release neurotransmitters by calcium-dependent exocytosis of synaptic vesicles. However, the molecular steps transducing the calcium signal into membrane fusion are still an enigma. It is reported here that synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids. This binding is specific for calcium and involves the cytoplasmic domain of synaptotagmin. Calcium binding is dependent on the intact oligomeric structure of synaptotagmin (it is abolished by proteolytic cleavage at a single site). These results suggest that synaptotagmin acts as a cooperative calcium receptor in exocytosis.
MeSH terms
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Animals
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Brain Chemistry*
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Calcium / metabolism*
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Calcium / pharmacology
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Calcium-Binding Proteins*
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Cell Membrane / metabolism
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Cytoplasmic Granules / metabolism
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Dansyl Compounds / metabolism
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Energy Transfer
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Exocytosis
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Fluorescent Dyes
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Liposomes / metabolism
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Macromolecular Substances
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / isolation & purification
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Membrane Glycoproteins / metabolism*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / isolation & purification
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Nerve Tissue Proteins / metabolism*
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Phosphatidylethanolamines / metabolism
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Rats
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Synaptic Vesicles / metabolism*
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Synaptotagmins
Substances
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Calcium-Binding Proteins
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Dansyl Compounds
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Fluorescent Dyes
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Liposomes
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Macromolecular Substances
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Phosphatidylethanolamines
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Synaptotagmins
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dansyl phosphatidylethanolamine
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Calcium