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Publication : Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+.

First Author  Sørensen JB Year  2003
Journal  J Gen Physiol Volume  122
Issue  3 Pages  265-76
PubMed ID  12939392 Mgi Jnum  J:105824
Mgi Id  MGI:3616733 Doi  10.1085/jgp.200308855
Citation  Sorensen JB, et al. (2003) Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+. J Gen Physiol 122(3):265-76
abstractText  We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2+ sensor for fast neurosecretion by analyzing the intracellular Ca2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the KD of Ca2+-dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca2+-threshold for secretion due to a twofold increase in the apparent KD of the Ca2+ sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca2+-dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca2+ dependence of exocytosis.
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