en
Scientific article
Review
Open access
English

ORP5 and ORP8: sterol sensors and phospholipid transfer proteins at membrane contact sites?

Published inBiomolecules, vol. 10, no. 6, 928
Publication date2020
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.

Keywords
  • Oxysterol binding protein like 5 and 8
  • OSBPL5
  • OSBPL8
  • PtdIns
  • PtdIns4P
  • PtdIns(4,5)P2
  • Cortical endoplasmic reticulum
Citation (ISO format)
CRIADO SANTOS, Nina, GIRIK, Vladimir, NUNES-HASLER, Paula. ORP5 and ORP8: sterol sensors and phospholipid transfer proteins at membrane contact sites? In: Biomolecules, 2020, vol. 10, n° 6, p. 928. doi: 10.3390/biom10060928
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal2218-273X
248views
138downloads

Technical informations

Creation07/21/2020 3:09:00 PM
First validation07/21/2020 3:09:00 PM
Update time03/15/2023 10:24:29 PM
Status update03/15/2023 10:24:28 PM
Last indexation02/12/2024 11:54:00 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack