Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides.
Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)-related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transfer of cholesterol and ergosterol between membranes in vitro. In addition, Osh4p transfers sterols more rapidly between membranes containing phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs. We confirmed this by showing that PM to ER sterol transport slows dramatically in mutants with conditional defects in PIP biosynthesis. Our findings argue that ORPs move sterols among cellular compartments and that sterol transport and intracellular distribution are regulated by PIPs.
Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD 20892, USA.
Sumana
S
Raychaudhuri
Young Jun
YJ
Im
James H
JH
Hurley
William A
WA
Prinz
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D004875:Ergosterol / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D011987:Receptors, Steroid; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
D002352:Carrier Proteins; D002784:Cholesterol; D004875:Ergosterol; D008081:Liposomes; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins