title: Osh4p is needed to reduce the level of phosphatidylinositol-4-phosphate on secretory vesicles as they mature.
abstract: Phosphatidylinositol-4-phosphate (PI4P) is produced on both the Golgi and the plasma membrane. Despite extensive vesicular traffic between these compartments, genetic analysis suggests that the two pools of PI4P do not efficiently mix with one another. Several lines of evidence indicate that the PI4P produced on the Golgi is normally incorporated into secretory vesicles, but the fate of that pool has been unclear. We show here that in yeast the oxysterol-binding proteins Osh1-Osh7 are collectively needed to maintain the normal distribution of PI4P and that Osh4p is critical in this function. Osh4p associates with secretory vesicles at least in part through its interaction with PI4P and is needed, together with lipid phosphatases, to reduce the level of PI4P as vesicles approach sites of exocytosis. This reduction in PI4P is necessary for a switch in the regulation of the Sec4p exchange protein, Sec2p, from an interaction with the upstream Rab, Ypt31/32, to an interaction with a downstream Sec4p effector, Sec15p. Spatial regulation of PI4P levels thereby plays an important role in vesicle maturation.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Yading
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Scott
authors.initials: S
authors.lastname: Hayano
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093 pnovick@ucsd.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Novick
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D060066:Protein Interaction Maps; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000098825:Oxysterol Binding Proteins
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins; C432935:OSH2 protein, S cerevisiae; C060862:SEC15 protein, S cerevisiae; C064456:SEC2 protein, S cerevisiae; C037178:phosphatidylinositol 4-phosphate; C121633:YPT32 protein, S cerevisiae; C064320:SEC4 protein, S cerevisiae