title: Sterol carrier protein-2 functions in phosphatidylinositol transfer and signaling.
abstract: Over 20 years ago, it was reported that liver cytosol contains at least two distinct proteins that transfer phosphatidylinositol in vitro, phosphatidylinositol transfer protein (PITP) and a pH 5.1 supernatant fraction containing sterol carrier protein-2 (SCP-2). In contrast to PITP, there has been minimal progress on the structural and functional significance of SCP-2 in phosphatidylinositol transport. As shown herein, highly purified, recombinant SCP-2 stimulated up to 13-fold the rapid (s) transfer of radiolabeled phosphatidylinositol (PI) from microsomal donor membranes to highly curved acceptor membranes. SCP-2 bound to microsomes in vitro and overexpression of SCP-2 in transfected L-cells resulted in the following: (i) redistribution of phosphatidylinositols from intracellular membranes (mitochondria and microsomes) to the plasma membrane; (ii) enhancement of insulin-mediated inositol-triphosphate production; and (iii) 5.5-fold down regulation of PITP. Like PITP, SCP-2 binds two ligands required for vesicle budding from the Golgi, PI, and fatty acyl CoA. Double immunolabeling confocal microscopy showed SCP-2 significantly colocalized with caveolin-1 in the cytoplasm (punctate) and plasma membrane of SCP-2 overexpressing hepatoma cells (72%), HT-29 cells (58%), and SCP-2 overexpressing L-cells (37%). Taken together, these data show for the first time that SCP-2 plays a hitherto unrecognized role in intracellular phosphatidylinositol transfer, distribution, and signaling.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, Texas 77843-4466, USA.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
authors.forename: Minglong
authors.initials: M
authors.lastname: Zhou
authors.forename: Christina L
authors.initials: CL
authors.lastname: Swaggerty
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.forename: Anca D
authors.initials: AD
authors.lastname: Petrescu
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Storey
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Martin
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: George M
authors.initials: GM
authors.lastname: Helmkamp
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ball
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D011994:Recombinant Proteins; C072087:sterol carrier proteins; D015544:Inositol 1,4,5-Trisphosphate