Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Compartmentation / physiology
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Cell Membrane / genetics
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Cell Membrane / metabolism*
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Cholesterol / metabolism
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum / metabolism*
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Ergosterol / metabolism
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Intracellular Membranes / metabolism
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Liposomes / chemistry
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Liposomes / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mutation / physiology
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Phosphatidylinositols / biosynthesis
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Phosphatidylinositols / metabolism*
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Receptors, Steroid
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Sterols / metabolism*
Substances
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Carrier Proteins
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KES1 protein, S cerevisiae
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Liposomes
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Membrane Proteins
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Phosphatidylinositols
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Receptors, Steroid
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Saccharomyces cerevisiae Proteins
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Sterols
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Cholesterol
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Ergosterol