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Science 2 February 2001:
Vol. 291. no. 5505, pp. 875 - 878
DOI: 10.1126/science.291.5505.875
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Reports

Control of Fusion Pore Dynamics During Exocytosis by Munc18

Richard J. Fisher,1 Jonathan Pevsner,2 Robert D. Burgoyne1*

Intracellular membrane fusion is mediated by the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. All vesicle transport steps also have an essential requirement for a member of the Sec1 protein family, including the neuronal Munc18-1 (also known as nSec1) in regulated exocytosis. Here, in adrenal chromaffin cells, we expressed a Munc18 mutant with reduced affinity for syntaxin, which specifically modified the kinetics of single-granule exocytotic release events, consistent with an acceleration of fusion pore expansion. Thus, Munc18 functions in a late stage in the fusion process, where its dissociation from syntaxin determines the kinetics of postfusion events.

1 Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
2 Department of Neurology, Kennedy Krieger Institute; and Department of Neuroscience, Johns Hopkins School of Medicine, 707 North Broadway, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: Burgoyne{at}liverpool.ac.uk

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