Oxysterol-Binding Proteins

  • Neale D. RidgwayEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 51)


In eukaryotic cells, membranes of the late secretory pathway contain a disproportionally large amount of cholesterol in relation to the endoplasmic reticulum, nuclear envelope and mitochondria. At one extreme, enrichment of the plasma membrane with cholesterol and sphingolipids is crucial for formation of liquid ordered domains (rafts) involved in cell communication and transport. On the other hand, regulatory machinery in the endoplasmic reticulum is maintained in a relatively cholesterol-poor environment, to ensure appropriate rapid responses to fluctuations in cellular sterol levels. Thus, cholesterol homeostasis is absolutely dependent on its distribution along an intracellular gradient. It is apparent that this gradient is maintained by a combination of sterol-lipid interactions, vesicular transport and sterol-binding/transport proteins. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, in particular the eukaryotic oxysterol binding protein (OSBP) family. Since the founding member of this family was identified more than 25 years ago, accumulated evidence implicates the 12-member family of OSBP and OSBP-related proteins (ORPs) in sterol signalling and/or sterol transport functions. The OSBP/ORP gene family is characterized by a conserved β-barrel sterol-binding fold but is differentiated from other sterol-binding proteins by the presence of additional domains that target multiple organelle membranes. Here we will discuss the functional and structural characteristics of the mammalian OSBP/ORP family that support a ‘dual-targeting’ model for sterol transport between membranes.


Cholesterol Endoplasmic reticulum Golgi apparatus Oxysterols Sterol transport 



ATP-binding cassette


acyl-CoA:cholesterol acyltransferase


amyloid precursor protein


ceramide transfer protein


endoplasmic reticulum


two phenylalanines in an acidic tract


low density lipoprotein


liver X receptor


Niemann-Pick C


OSBP-homology domain


oxysterol binding protein


OSBP-related protein


nuclear-vacuolar junction


phosphoinositide-dependent kinase


phosphatidylinositol phosphate


phosphatidylinositol 4-phosphate

PI4, 5P2

phosphatidylinositol 4,5-bisphosphate


pleckstrin homology


plasma membrane


protein phosphatase 2A


RNA interference


sterol-regulatory element binding protein




steroidogenic acute regulatory transport


vesicle-associated membrane protein-associated protein


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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Departments of Pediatrics and Biochemistry & Molecular BiologyAtlantic Research Centre, Dalhousie UniversityNova ScotiaCanada

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