title: Control of transmembrane lipid asymmetry in chromaffin granules by an ATP-dependent protein.
abstract: The Ca2+-dependent binding of annexin proteins to secretory granule membranes seems to be involved in the early stage of exocytosis. Binding studies have shown that these proteins have a specificity for phosphatidylserine (PtdS) interfaces. Furthermore, aminolipids are necessary for contact and fusion between lipid vesicles or between liposomes and chromaffin granules. Thus, PtdS must be present on the granule outer (cytoplasmic) monolayer. We report here that chromaffin granules possess a mechanism to maintain PtdS orientation, comparable to the ATP-dependent aminophospholipid translocase from human erythrocytes. The translocase, in granules, selectively transports PtdS from the luminal to the cytoplasmic monolayer, provided the incubation medium contains ATP. As this protein shares several properties with the granule vanadate-sensitive ATPase II, we infer that this ATPase, of relative molecular mass 115,000, is the protein responsible for aminophospholipid translocation. This is the first evidence for an ATP-dependent specific phospholipid 'flippase' in intracellular organelles.
authors.affiliation: Institut de Biologie Physico-Chimique, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Zachowski
authors.forename: J P
authors.initials: JP
authors.lastname: Henry
authors.forename: P F
authors.initials: PF
authors.lastname: Devaux
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002837:Chromaffin Granules / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005033:Ethylmaleimide / Q000494:pharmacology; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D010713:Phosphatidylcholines; D000255:Adenosine Triphosphate; D005033:Ethylmaleimide