ORP5 and ORP8: Sterol Sensors and Phospholipid Transfer Proteins at Membrane Contact Sites?
Open Access
- 18 June 2020
- journal article
- review article
- Published by MDPI AG in Biomolecules
- Vol. 10 (6), 928
- https://doi.org/10.3390/biom10060928
Abstract
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.This publication has 73 references indexed in Scilit:
- Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid MetabolismPLOS ONE, 2013
- Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayersThe Journal of cell biology, 2011
- OSBP-Related Protein 8 (ORP8) Regulates Plasma and Liver Tissue Lipid Levels and Interacts with the Nucleoporin Nup62PLOS ONE, 2011
- A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol traffickingThe Journal of cell biology, 2011
- The Diverse Functions of Oxysterol-Binding ProteinsAnnual Review of Cell and Developmental Biology, 2010
- Lipids and Cholesterol as Regulators of Traffic in the Endomembrane SystemAnnual Review of Biophysics, 2010
- Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologuesThe Journal of cell biology, 2009
- The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocketBiochemical Journal, 2007
- Cholesterol Sensing, Trafficking, and EsterificationAnnual Review of Cell and Developmental Biology, 2006
- Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositidesThe Journal of cell biology, 2006