Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2
We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increas...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2003 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/17816 |
| Acceso en línea: | http://hdl.handle.net/11441/17816 https://doi.org/10.1085/jgp.200308855 |
| Access Level: | acceso abierto |
| Palabra clave: | Chromaffin cell Membrane fusion Neurosecretion Capacitance measurement Amperometry |
| Sumario: | We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ 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 K D of Ca 2 + - 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 Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis. |
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