title: Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion.
abstract: The Ca(2+)-triggered merger of two apposed membranes is the defining step of regulated exocytosis. CHOL is required at critical levels in secretory vesicle membranes to enable efficient, native membrane fusion: CHOL-sphingomyelin enriched microdomains organize the site and regulate fusion efficiency, and CHOL directly supports the capacity for membrane merger by virtue of its negative spontaneous curvature. Specific, structurally dissimilar lipids substitute for CHOL in supporting the ability of vesicles to fuse: diacylglycerol, alphaT, and phosphatidylethanolamine support triggered fusion in CHOL-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 spontaneous curvature. Such a local lipid composition is energetically favorable, ensuring the necessary "spontaneous" lipid rearrangements that must occur during native membrane fusion-Ca(2+)-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.
authors.affiliation: Department of Physiology and Biophysics, Department of Biochemistry and Molecular Biology, Department of Cell Biology and Anatomy, and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Churchward
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rogasevskaia
authors.forename: David M
authors.initials: DM
authors.lastname: Brandman
authors.forename: Houman
authors.initials: H
authors.lastname: Khosravani
authors.forename: Phillip
authors.initials: P
authors.lastname: Nava
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Atkinson
authors.forename: Jens R
authors.initials: JR
authors.lastname: Coorssen
mesh_terms: D002118:Calcium / Q000737:chemistry*; D003198:Computer Simulation; D008560:Membrane Fluidity; D008561:Membrane Fusion; D008956:Models, Chemical; D010743:Phospholipids / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D010743:Phospholipids; D002118:Calcium