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Science. 2015 Jul 24;349(6246):428-32. doi: 10.1126/science.aab1370.

INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.

Author information

1
Department of Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, and Program for Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06520, USA.
2
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
3
Department of Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, and Program for Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06520, USA. pietro.decamilli@yale.edu nakatsu@med.niigata-u.ac.jp.

Abstract

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 delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

PMID:
26206935
PMCID:
PMC4638224
DOI:
10.1126/science.aab1370
[Indexed for MEDLINE]
Free PMC Article

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