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Mol Biol Cell. 2014 Oct 15;25(20):3195-209. doi: 10.1091/mbc.E14-07-1229. Epub 2014 Aug 20.

Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension.

Author information

1
Université Paris Descartes, Sorbonne Paris Cité, Centre National de la Recherche Scientifique, UMR 8250, 75270 Paris Cedex 06, France Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, 75005 Paris, France.
2
Université Paris Descartes, Sorbonne Paris Cité, Centre National de la Recherche Scientifique, UMR 8250, 75270 Paris Cedex 06, France.
3
Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, 75005 Paris, France.
4
Institut Curie, Paris 75248, France Institut National de la Santé et de la Recherche Médicale, U900, Paris 75248, France Ecole des Mines ParisTech, Fontainebleau, 77300 France.
5
Centre National de la Recherche Scientifique/UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Université Strasbourg, 67084 Strasbourg, France.
6
Université Paris Descartes, Sorbonne Paris Cité, Centre National de la Recherche Scientifique, UMR 8250, 75270 Paris Cedex 06, France Francois.Darchen@parisdescartes.fr.

Abstract

Membrane fusion underlies multiple processes, including exocytosis of hormones and neurotransmitters. Membrane fusion starts with the formation of a narrow fusion pore. Radial expansion of this pore completes the process and allows fast release of secretory compounds, but this step remains poorly understood. Here we show that inhibiting the expression of the small GTPase Cdc42 or preventing its activation with a dominant negative Cdc42 construct in human neuroendocrine cells impaired the release process by compromising fusion pore enlargement. Consequently the mode of vesicle exocytosis was shifted from full-collapse fusion to kiss-and-run. Remarkably, Cdc42-knockdown cells showed reduced membrane tension, and the artificial increase of membrane tension restored fusion pore enlargement. Moreover, inhibiting the motor protein myosin II by blebbistatin decreased membrane tension, as well as fusion pore dilation. We conclude that membrane tension is the driving force for fusion pore dilation and that Cdc42 is a key regulator of this force.

PMID:
25143404
PMCID:
PMC4196869
DOI:
10.1091/mbc.E14-07-1229
[Indexed for MEDLINE]
Free PMC Article

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