title: Anionic lipids in Ca(2+)-triggered fusion.
abstract: Anionic lipids are native membrane components that have a profound impact on many cellular processes, including regulated exocytosis. Nonetheless, the full nature of their contribution to the fast, Ca(2+)-triggered fusion pathway remains poorly defined. Here we utilize the tightly coupled quantitative molecular and functional analyses enabled by the cortical vesicle model system to elucidate the roles of specific anionic lipids in the docking, priming and fusion steps of regulated release. Studies with cholesterol sulfate established that effectively localized anionic lipids could contribute to Ca(2+)-sensing and even bind Ca(2+) directly as effectors of necessary membrane rearrangements. The data thus support a role for phosphatidylserine in Ca(2+) sensing. In contrast, phosphatidylinositol would appear to serve regulatory functions in the physiological fusion machine, contributing to priming and thus the modulation and tuning of the fusion process. We note the complexities associated with establishing the specific roles of (anionic) lipids in the native fusion mechanism, including their localization and interactions with other critical components that also remain to be more clearly and quantitatively defined.
authors.affiliation: Department of Chemical & Biological Sciences, Mount Royal University, 4825 Mount Royal Gate SW, Calgary, AB, T3E 6K6 Canada.
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Rogasevskaia
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Churchward
authors.forename: Jens R
authors.initials: JR
authors.lastname: Coorssen
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry; D002118:Calcium / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects*; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D047270:Strongylocentrotus purpuratus / Q000378:metabolism
chemical_list: D000838:Anions; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D002784:Cholesterol; D009355:Neomycin; D002118:Calcium