Sterol Carrier Protein-2 Functions in Phosphatidylinositol Transfer and Signaling † Academic Article uri icon

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.

published proceedings

  • Biochemistry

author list (cited authors)

  • Schroeder, F., Zhou, M., Swaggerty, C. L., Atshaves, B. P., Petrescu, A. D., Storey, S. M., ... Ball, J. M.

citation count

  • 24

complete list of authors

  • Schroeder, Friedhelm||Zhou, Minglong||Swaggerty, Christina L||Atshaves, Barbara P||Petrescu, Anca D||Storey, Stephen M||Martin, Gregory G||Huang, Huan||Helmkamp, George M||Ball, Judith M

publication date

  • March 2003