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Synaptotagmin I Functions as a Calcium Sensor to Synchronize Neurotransmitter Release

To characterize Ca 2+-mediated synaptic vesicle fusion, we analyzed Drosophila synaptotagmin I mutants deficient in specific interactions mediated by its two Ca 2+ binding C2 domains. In the absence of synaptotagmin I, synchronous release is abolished and a kinetically distinct delayed asynchronous...

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Published in:Neuron (Cambridge, Mass.) Mass.), 2002-12, Vol.36 (5), p.897-908
Main Authors: Yoshihara, Motojiro, Littleton, J.Troy
Format: Article
Language:English
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Summary:To characterize Ca 2+-mediated synaptic vesicle fusion, we analyzed Drosophila synaptotagmin I mutants deficient in specific interactions mediated by its two Ca 2+ binding C2 domains. In the absence of synaptotagmin I, synchronous release is abolished and a kinetically distinct delayed asynchronous release pathway is uncovered. Synapses containing only the C2A domain of synaptotagmin partially recover synchronous fusion, but have an abolished Ca 2+ cooperativity. Mutants that disrupt Ca 2+ sensing by the C2B domain have synchronous release with normal Ca 2+ cooperativity, but with reduced release probability. Our data suggest the Ca 2+ cooperativity of neurotransmitter release is likely mediated through synaptotagmin-SNARE interactions, while phospholipid binding and oligomerization trigger rapid fusion with increased release probability. These results indicate that synaptotagmin is the major Ca 2+ sensor for evoked release and functions to trigger synchronous fusion in response to Ca 2+, while suppressing asynchronous release.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(02)01065-6