PT - JOURNAL ARTICLE AU - Wang, Chih-Tien AU - Grishanin, Ruslan AU - Earles, Cynthia A. AU - Chang, Payne Y. AU - Martin, Thomas F. J. AU - Chapman, Edwin R. AU - Jackson, Meyer B. TI - Synaptotagmin Modulation of Fusion Pore Kinetics in Regulated Exocytosis of Dense-Core Vesicles AID - 10.1126/science.1064002 DP - 2001 Nov 02 TA - Science PG - 1111--1115 VI - 294 IP - 5544 4099 - http://science.sciencemag.org/content/294/5544/1111.short 4100 - http://science.sciencemag.org/content/294/5544/1111.full SO - Science2001 Nov 02; 294 AB - In the exocytosis of neurotransmitter, fusion pore opening represents the first instant of fluid contact between the vesicle lumen and extracellular space. The existence of the fusion pore has been established by electrical measurements, but its molecular composition is unknown. The possibility that synaptotagmin regulates fusion pores was investigated with amperometry to monitor exocytosis of single dense-core vesicles. Overexpression of synaptotagmin I prolonged the time from fusion pore opening to dilation, whereas synaptotagmin IV shortened this time. Both synaptotagmin isoforms reduced norepinephrine flux through open fusion pores. Thus, synaptotagmin interacts with fusion pores, possibly by associating with a core complex of membrane proteins and/or lipid.