The oxysterol binding protein Kes1p regulates Golgi apparatus phosphatidylinositol-4-phosphate function.
The Saccharomyces cerevisiae phosphatidylcholine/phosphatidylinositol transfer protein Sec14p is required for Golgi apparatus-derived vesicular transport through coordinate regulation of phospholipid metabolism. Sec14p is normally essential. The essential requirement for SEC14 can be bypassed by inactivation of (i) the CDP-choline pathway for phosphatidylcholine synthesis or (ii) KES1, which encodes an oxysterol binding protein. A unique screen was used to determine genome-wide genetic interactions for the essential gene SEC14 and to assess whether the two modes of "sec14 bypass" were similar or distinct. The results indicate that inactivation of the CDP-choline pathway allows cells with inactivated SEC14 to live through a mechanism distinct from that of inactivation of KES1. We go on to demonstrate an important biological function of Kes1p. Kes1p regulates Golgi apparatus-derived vesicular transport by inhibiting the function of Pik1p-generated Golgi apparatus phosphatidylinositol-4-phosphate (PI-4P). Kes1p affects both the availability and level of Golgi apparatus PI-4P. A set of potential PI-4P-responsive proteins that include the Rab GTPase Ypt31p and its GTP exchange factor are described.
Fairn
Gregory D
GD
Department of Pediatrics, Dalhousie University, Halifax, NS, Canada B3H 4H7.
Curwin
Amy J
AJ
Stefan
Christopher J
CJ
McMaster
Christopher R
CR
D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry; D016681:Genome, Fungal; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry; D049294:Phospholipid Transfer Proteins / Q000737:chemistry; D011987:Receptors, Steroid; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013261:Sterols / Q000737:chemistry; D043324:beta-Fructofuranosidase / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000098825:Oxysterol Binding Proteins
D019870:1-Phosphatidylinositol 4-Kinase; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D043324:beta-Fructofuranosidase; D020691:rab GTP-Binding Proteins; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins; C483438:SEC14 protein, S cerevisiae; C037178:phosphatidylinositol 4-phosphate; C441760:PIK1 protein, S cerevisiae; C087905:YPT31 protein, S cerevisiae