Oxysterol binding proteins: in more than one place at one time?
Oxysterols are potent signalling lipids that directly bind liver X receptors (LXRs) and a subset of oxysterol binding protein (OSBP) related proteins (ORPs). It is relatively well established that the oxysterol-regulated function of LXRs is to control the expression of genes involved in reverse cholesterol transport, catabolism of cholesterol, and lipogenesis. In contrast, the mechanisms by which oxysterols and ORPs affect cellular lipid metabolism have remained poorly understood. In this review, we summarize the information available on function of the ORPs and compare the two families of proteins binding oxysterol to demonstrate the different responses that similar lipids can elicit within cells. The other focus is on the membrane targeting determinants and the protein interaction partners of ORPs, which provide interesting clues to the mode(s) of ORP action. Specifically, we suggest a model in which a general property of ORPs is to function at membrane contact sites, specialized zones of communication between two different organelles.
Olkkonen
Vesa M
VM
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland. vesa.olkkonen@ktl.fi
Levine
Timothy P
TP
D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008954:Models, Biological; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013261:Sterols / Q000737:chemistry / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013261:Sterols; D000098825:Oxysterol Binding Proteins; D002784:Cholesterol