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Science 2 November 2001:
Vol. 294. no. 5544, pp. 1111 - 1115
DOI: 10.1126/science.1064002
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Reports

Synaptotagmin Modulation of Fusion Pore Kinetics in Regulated Exocytosis of Dense-Core Vesicles

Chih-Tien Wang,1 Ruslan Grishanin,2 Cynthia A. Earles,1 Payne Y. Chang,1 Thomas F. J. Martin,2 Edwin R. Chapman,1 Meyer B. Jackson1*

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.

1 Department of Physiology, University of Wisconsin Medical School,
2 Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
*   To whom correspondence should be addressed. E-mail: mjackson{at}physiology.wisc.edu

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