title: The counterflow transport of sterols and PI4P.
abstract: Cholesterol levels in intracellular membranes are constantly adjusted to match with specific organelle functions. Cholesterol is kept high in the plasma membrane (PM) because it is essential for its barrier function, while low levels are found in the endoplasmic reticulum (ER) where cholesterol mediates feedback control of its own synthesis by sterol-sensor proteins. The ER→Golgi→PM concentration gradient of cholesterol in mammalian cells, and ergosterol in yeast, appears to be sustained by specific intracellular transport processes, which are mostly mediated by lipid transfer proteins (LTPs). Here we review a recently described function of two LTPs, OSBP and its yeast homolog Osh4p, which consists in creating a sterol gradient between membranes by vectorial transport. OSBP also contributes to the formation of ER/Golgi membrane contact sites, which are important hubs for the transfer of several lipid species. OSBP and Osh4p organize a counterflow transport of lipids whereby sterols are exchanged for the phosphoinositide PI4P, which is used as a fuel to drive sterol transport. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 06560 Valbonne, France. Electronic address: mesmin@ipmc.cnrs.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Mesmin
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 06560 Valbonne, France. Electronic address: antonny@ipmc.cnrs.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Antonny
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
chemical_list: D002352:Carrier Proteins; C087901:KES1 protein, S cerevisiae; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; C030363:lipid transfer protein; D000098825:Oxysterol Binding Proteins; C037178:phosphatidylinositol 4-phosphate; D002784:Cholesterol
keywords: Cholesterol; Lipid transfer protein; Membrane contact site; OSBP; Osh4p; PI4P