title: INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.
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.
authors.affiliation: 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.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
authors.forename: Federico
authors.initials: F
authors.lastname: Torta
authors.affiliation: 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.
authors.forename: Kaori
authors.initials: K
authors.lastname: Masai
authors.affiliation: 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.
authors.forename: Louise
authors.initials: L
authors.lastname: Lucast
authors.affiliation: 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.
authors.forename: Heather
authors.initials: H
authors.lastname: Czapla
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
authors.forename: Lukas B
authors.initials: LB
authors.lastname: Tanner
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Narayanaswamy
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.affiliation: 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.
authors.forename: Fubito
authors.initials: F
authors.lastname: Nakatsu
authors.affiliation: 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.
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
chemical_list: D018129:Phosphatidylinositol Phosphates; D010718:Phosphatidylserines; D011987:Receptors, Steroid; D000098825:Oxysterol Binding Proteins; C037178:phosphatidylinositol 4-phosphate