Sterol carrier protein-2: new roles in regulating lipid rafts and signaling.
Sterol carrier protein-2 (SCP-2) was independently discovered as a soluble protein that binds and transfers cholesterol as well as phospholipids (nonspecific lipid transfer protein, nsLTP) in vitro. Physiological functions of this protein are only now beginning to be resolved. The gene encoding SCP-2 also encodes sterol carrier protein-x (SCP-x) arising from an alternate transcription site. In vitro and in vivo SCP-x serves as a peroxisomal 3-ketoacyl-CoA thiolase in oxidation of branched-chain lipids (cholesterol to form bile acids; branched-chain fatty acid for detoxification). While peroxisomal SCP-2 facilitates branched-chain lipid oxidation, the role(s) of extraperoxisomal (up to 50% of total) are less clear. Studies using transfected fibroblasts overexpressing SCP-2 and hepatocytes from SCP-2/SCP-x gene-ablated mice reveal that SCP-2 selectively remodels the lipid composition, structure, and function of lipid rafts/caveolae. Studies of purified SCP-2 and in cells show that SCP-2 has high affinity for and selectively transfers many lipid species involved in intracellular signaling: fatty acids, fatty acyl CoAs, lysophosphatidic acid, phosphatidylinositols, and sphingolipids (sphingomyelin, ceramide, mono-di-and multi-hexosylceramides, gangliosides). SCP-2 selectively redistributes these signaling lipids between lipid rafts/caveolae and intracellular sites. These findings suggest SCP-2 serves not only in cholesterol and phospholipid transfer, but also in regulating multiple lipid signaling pathways in lipid raft/caveolae microdomains of the plasma membrane.
Schroeder
Friedhelm
F
Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, USA. Fschroeder@cvm.tamu.edu
Atshaves
Barbara P
BP
McIntosh
Avery L
AL
Gallegos
Adalberto M
AM
Storey
Stephen M
SM
Parr
Rebecca D
RD
Jefferson
John R
JR
Ball
Judith M
JM
Kier
Ann B
AB
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D013261:Sterols / Q000378:metabolism; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D005227:Fatty Acids; D008563:Membrane Lipids; D013261:Sterols; C072087:sterol carrier proteins; D002784:Cholesterol