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Sterol carrier protein-2: new roles in regulating lipid rafts and signaling

Sterol carrier protein-2: new roles in regulating lipid rafts and signaling

Biochimica et Biophysica Acta 1771(6): 700-718

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.

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Accession: 017129650

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PMID: 17543577

DOI: 10.1016/j.bbalip.2007.04.005

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