Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion.
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.
Churchward
Matthew A
MA
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.
Rogasevskaia
Tatiana
T
Brandman
David M
DM
Khosravani
Houman
H
Nava
Phillip
P
Atkinson
Jeffrey K
JK
Coorssen
Jens R
JR
D002118:Calcium / Q000737:chemistry*; D003198:Computer Simulation; D008560:Membrane Fluidity; D008561:Membrane Fusion; D008956:Models, Chemical; D010743:Phospholipids / Q000737:chemistry*; D013499:Surface Properties
D010743:Phospholipids; D002118:Calcium