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Cellular and Molecular Life Sciences

, Volume 75, Issue 17, pp 3079–3098 | Cite as

Bridging the molecular and biological functions of the oxysterol-binding protein family

  • Antonietta Pietrangelo
  • Neale D. Ridgway
Review

Abstract

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation. This unique subcellular location, coupled with diverse ligand preferences and tissue distribution, has identified OSBP/ORPs as key arbiters of membrane composition and function. Here, we will review how molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions.

Keywords

Oxysterol-binding proteins Membrane contact sites Intracellular lipid transport Cancer Dyslipidemia Metabolism Viral replication 

Abbreviations

ALS

Amyotrophic lateral sclerosis

ABC

ATP binding cassette

CARTS

Carriers of the trans-Golgi network to the cell surface

CERT

Ceramide transfer protein

ER

Endoplasmic reticulum

FFAT

Two phenylalanines in an acidic tract

HDL

High density lipoprotein

25OH

25-Hydroxycholesterol

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

LDL

Low density lipoprotein

LEL

Late endosomes–lysosomes

LD

Lipid droplet

LRH-1

Liver receptor homolog-1

LXR

Liver X receptor

LTP

Lipid transfer protein

MCS

Membrane contact site

mTOR

Mammalian target of rapamycin

NPC

Niemann–Pick type C

OSBP

Oxysterol-binding protein

ORP

OSBP-related protein

OHD

OSBP homology domain

Osh

Oxysterol-binding protein homolog

PM

Plasma membrane

PI4K

Phosphatidylinositol-4-kinase

PI

Phosphatidylinositol

PI(4)P

Phosphatidylinositol 4-phosphate

PIPs

Phosphatidylinositol phosphates

PLC

Phospholipase C

PS

Phosphatidylserine

RILP

Rab7-interacting lysosomal protein

SM

Sphingomyelin

SNP

Single nucleotide polymorphisms

SREBP

Sterol regulatory element binding protein

TGN

Trans-Golgi network

VAP

Vesicle-associated membrane protein-associated protein

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Atlantic Research Center, C306 CRC Bldg, Department of Pediatrics, and Biochemistry and Molecular BiologyDalhousie UniversityHalifaxCanada

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