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| http://purl.uniprot.org/citations/22279210 | http://www.w3.org/2000/01/rdf-schema#comment | "Synaptotagmin is the major calcium sensor for fast synaptic transmission that requires the synchronous fusion of synaptic vesicles. Synaptotagmin contains two calcium-binding domains: C2A and C2B. Mutation of a positively charged residue (R233Q in rat) showed that Ca2+-dependent interactions between the C2A domain and membranes play a role in the electrostatic switch that initiates fusion. Surprisingly, aspartate-to-asparagine mutations in C2A that inhibit Ca2+ binding support efficient synaptic transmission, suggesting that Ca2+ binding by C2A is not required for triggering synchronous fusion. Based on a structural analysis, we generated a novel mutation of a single Ca2+-binding residue in C2A (D229E in Drosophila) that inhibited Ca2+ binding but maintained the negative charge of the pocket. This C2A aspartate-to-glutamate mutation resulted in ∼80% decrease in synchronous transmitter release and a decrease in the apparent Ca2+ affinity of release. Previous aspartate-to-asparagine mutations in C2A partially mimicked Ca2+ binding by decreasing the negative charge of the pocket. We now show that the major function of Ca2+ binding to C2A is to neutralize the negative charge of the pocket, thereby unleashing the fusion-stimulating activity of synaptotagmin. Our results demonstrate that Ca2+ binding by C2A is a critical component of the electrostatic switch that triggers synchronous fusion. Thus, Ca2+ binding by C2B is necessary and sufficient to regulate the precise timing required for coupling vesicle fusion to Ca2+ influx, but Ca2+ binding by both C2 domains is required to flip the electrostatic switch that triggers efficient synchronous synaptic transmission."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.4652-11.2012"xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Chapman E.R."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Wang Z."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Sutton R.B."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Evans C.S."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Reist N.E."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Striegel A.R."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Biela L.M."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/author | "Delehoy J.B."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/pages | "1253-1260"xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/title | "Calcium binding by synaptotagmin's C2A domain is an essential element of the electrostatic switch that triggers synchronous synaptic transmission."xsd:string |
| http://purl.uniprot.org/citations/22279210 | http://purl.uniprot.org/core/volume | "32"xsd:string |
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