PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts

Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus…

• AF
  Agency for Science, Technology and Research
• NU
  National University of Singapore
• NI
  National Institutes of Health

  Awards: DA018343, DK45735, R37NS036251, DK082700
• LS
  Life Sciences Institute
• SA
  Science and Engineering Research Council

  Award: BMRC-SERC 112 148 0006
• BR
  Biomedical Research Council