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Biophys. J. BioFAST: First Published January 28, 2008. doi:10.1529/biophysj.107.123984
© 2008 by the Biophysical Society.

A more recent version of this article appeared on May 15, 2008.
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MEMBRANES

Specific lipids supply critical intrinsic negative curvature - an essential component of native Ca2+-triggered membrane fusion

Matthew A Churchward 1, Tatiana Rogasevskaia 1, David M Brandman 1, Houman Khosravani 1, Phillip Nava 2, Jeffrey K Atkinson 2 and Jens Coorssen 3*

1 University of Calgary
2 Brock University
3 University of Calgary / Hotchkiss Brain Institute

* To whom correspondence should be addressed. E-mail: jcoorsse{at}ucalgary.ca.

Submitted on October 17, 2007
Revised on December 7, 2007
Accepted on 27 December 2007


  Abstract
The Ca2+-triggered merger of two apposed membranes is the defining step of regulated exocytosis. Cholesterol is required at critical levels in secretory vesicle membranes to enable efficient, native membrane fusion: cholesterol-sphingomyelin enriched microdomains organize the site and regulate fusion efficiency, and cholesterol directly supports the capacity for membrane merger by virtue of its intrinsic negative curvature. Specific, structurally dissimilar lipids substitute for cholesterol in supporting the ability of vesicles to fuse: diacylglycerol, {alpha}-tocopherol, and phosphatidylethanolamine support triggered fusion in cholesterol-depleted vesicles and this correlates quantitatively with the amount of curvature each imparts to the membrane. Lipids of lesser negative curvature than cholesterol do not support fusion. The fundamental mechanism of regulated bilayer merger requires not only a defined amount of membrane negative curvature, but this curvature must be provided by molecules having a specific, critical intrinsic curvature. Such a local lipid composition is energetically favourable, ensuring the necessary 'spontaneous' lipid rearrangements that must occur during native membrane fusion - Ca2+-triggered fusion pore formation and expansion. Thus, different fusion sites or vesicle types can use specific alternate lipidic components, or combinations thereof, to facilitate and modulate the fusion pore.

Key Words: cholesterol, diacylglycerol, diacylphosphatidylethanolamine, exocytosis, tocopherol, vesicle




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Copyright © 2008 by the Biophysical Society.