Abstract
Synaptic vesicle fusion at synapses is triggered by increases in cytosolic Ca2+ levels. However, the identity of the Ca2+ sensor and the transduction mechanism of the Ca2+ trigger are unknown. We show that Complexins, stoichiometric components of the exocytotic core complex, are important regulators of transmitter release at a step immediately preceding vesicle fusion. Neurons lacking Complexins show a dramatically reduced transmitter release efficiency due to decreased Ca2+ sensitivity of the synaptic secretion process. Analyses of mutant neurons demonstrate that Complexins are acting at or following the Ca2+-triggering step of fast synchronous transmitter release by regulating the exocytotic Ca2+ sensor, its interaction with the core complex fusion machinery, or the efficiency of the fusion apparatus itself.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Vesicular Transport
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Animals
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Calcimycin / pharmacology
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Calcium / metabolism*
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Cells, Cultured
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Gene Deletion
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Hippocampus / cytology
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Ionophores / pharmacology
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Mice
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Mice, Mutant Strains
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Microscopy, Electron
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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Neuronal Plasticity / physiology
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Neurons / physiology
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Neurons / ultrastructure
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Neurotransmitter Agents / metabolism*
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Patch-Clamp Techniques
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Synaptic Vesicles / physiology
Substances
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Adaptor Proteins, Vesicular Transport
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Ionophores
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Nerve Tissue Proteins
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Neurotransmitter Agents
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complexin I
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complexin II
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Calcimycin
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Calcium