title: INTRACELLULAR TRANSPORT. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate.
abstract: In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the crystal structure of Osh6p:PI4P complex and demonstrated that the transport of PS by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P-phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove PS transport. Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Moser von Filseck
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Alenka
authors.initials: A
authors.lastname: Čopič
authors.affiliation: Inserm U1054, 29 rue de Navacelles, 34090 Montpellier, France. CNRS UMR5048, Centre de Biochimie Structurale, 29 rue de Navacelles, 34090 Montpellier, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Delfosse
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vanni
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Jackson
authors.affiliation: Inserm U1054, 29 rue de Navacelles, 34090 Montpellier, France. CNRS UMR5048, Centre de Biochimie Structurale, 29 rue de Navacelles, 34090 Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Bourguet
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France. drin@ipmc.cnrs.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drin
mesh_terms: D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
chemical_list: D018129:Phosphatidylinositol Phosphates; D010718:Phosphatidylserines; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D000098825:Oxysterol Binding Proteins; C037178:phosphatidylinositol 4-phosphate; C081864:SAC1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases