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

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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.

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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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    Antonietta Pietrangelo & Neale D. Ridgway

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Pietrangelo, A., Ridgway, N.D. Bridging the molecular and biological functions of the oxysterol-binding protein family. Cell. Mol. Life Sci. 75, 3079–3098 (2018). https://doi.org/10.1007/s00018-018-2795-y

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