title: Saposin C induces pH-dependent destabilization and fusion of phosphatidylserine-containing vesicles.
abstract: We have previously shown that saposin C (Sap C), a glucosylceramidase activator protein, interacts with phosphatidylserine (PS) large unilamellar vesicles (LUV), promoting the glucosylceramidase binding to the bilayer [(1993) FEBS Lett. 336, 159-162]. In the present paper the consequences of the Sap C interaction on the lipid organization of the vesicles are reported. It was found that Sap C perturbs the PS bilayer as shown by the release of an encapsulated fluorescent dye. Three different procedures, resonance energy transfer, gel filtration and electron microscopy, indicated that the activator protein is also able to make PS liposomes fuse. The effects of Sap C on PS vesicles were observed at low but not at neutral pH. The lipid composition of the bilayer also affected the Sap C-induced destabilization; in fact, the presence of PS in mixed LUV was essential for significant leakage to occur. These results demonstrate for the first time that Sap C is a protein capable of destabilizing and fusing acidic phospholipid-containing membranes in a pH-dependent fashion.
authors.affiliation: Department of Metabolism and Pathological Biochemistry, Istituto Superiore Sanità, Roma, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Vaccaro
authors.forename: M
authors.initials: M
authors.lastname: Tatti
authors.forename: F
authors.initials: F
authors.lastname: Ciaffoni
authors.forename: R
authors.initials: R
authors.lastname: Salvioli
authors.forename: A
authors.initials: A
authors.lastname: Serafino
authors.forename: A
authors.initials: A
authors.lastname: Barca
mesh_terms: D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D004789:Enzyme Activation; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes; D008560:Membrane Fluidity; D008561:Membrane Fusion; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D049231:Saposins; D001617:beta-Glucosidase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D008051:Lipid Bilayers; D008081:Liposomes; D010718:Phosphatidylserines; D049231:Saposins; D001617:beta-Glucosidase