The OSBP-related proteins: a novel protein family involved in vesicle transport,cellular lipid metabolism,and cell signalling |
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Authors: | Markku Lehto Vesa M Olkkonen |
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Institution: | Department of Molecular Medicine, National Public Health Institute, Biomedicum, P.O. Box 104, Haartmaninkatu 8, FIN-00251 Helsinki, Finland |
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Abstract: | Proteins/genes showing high sequence homology to the mammalian oxysterol binding protein (OSBP) have been identified in a variety of eukaryotic organisms from yeast to man. The unifying feature of the gene products denoted as OSBP-related proteins (ORPs) is the presence of an OSBP-type ligand binding (LB) domain. The LB domains of OSBP and its closest homologue bind oxysterols, while data on certain other family members suggest interaction with phospholipids. Many ORPs also have a pleckstrin homology (PH) domain in the amino-terminal region. The PH domains of the family members studied in detail are known to interact with membrane phosphoinositides and play an important role in the intracellular targeting of the proteins. It is plausible that the ORPs constitute a regulatory apparatus that senses the status of specific lipid ligands in membranes, using the PH and/or LB domains, and mediates information to yet poorly known downstream machineries. Functional studies carried out on the ORP proteins in different organisms indicate roles of the gene family in diverse cellular processes including control of lipid metabolism, regulation of vesicle transport, and cell signalling events. |
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Keywords: | Cell signalling Cholesterol metabolism Membrane trafficking ORP Oxysterol binding protein Pleckstrin homology domain Protein family ACAT acyl-coenzyme A cholesterol acyltransferase ARF adenosinediphosphate ribosylation factor CHO Chinese hamster ovary (cell line) ER endoplasmic reticulum GTPase guanosinetriphosphatase HMG-CoA 3-hydroxy-3-methylglutaryl coenzyme A LB ligand binding LDL low-density lipoprotein 25-OHC 25-hydroxycholesterol ORP OSBP-related protein OSBP oxysterol binding protein Osh (yeast) OSBP homologue PC phosphatidylcholine PI phosphatidylinositol PI(4)P phosphatidylinositol-4-phosphate PH pleckstrin homology SREBP sterol regulatory element binding protein VSVG vesicular stomatitis virus G protein |
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