@article{999a8350fb7111de825d000ea68e967b,
title = "Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+",
abstract = "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.",
author = "S{\o}rensen, {Jakob B} and Rafael Fern{\'a}ndez-Chac{\'o}n and S{\"u}dhof, {Thomas C} and Erwin Neher",
note = "Keywords: Animals; Arginine; Calcium; Calcium-Binding Proteins; Chromaffin Cells; Differential Threshold; Electric Capacitance; Exocytosis; Glutamine; Intracellular Membranes; Membrane Glycoproteins; Mice; Mice, Mutant Strains; Nerve Tissue Proteins; Phospholipids; Point Mutation; Secretory Vesicles; Synaptotagmin I; Synaptotagmins; Time Factors",
year = "2003",
doi = "10.1085/jgp.200308855",
language = "English",
volume = "122",
pages = "265--76",
journal = "Journal of General Physiology",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "3",
}