title: Metabolic activation of the HOG MAP kinase pathway by Snf1/AMPK regulates lipid signaling at the Golgi.
abstract: Phosphatidylinositol-4-phosphate (PI(4)P) is an important regulator of Golgi function. Metabolic regulation of Golgi PI(4)P requires the lipid phosphatase Sac1 that translocates between endoplasmic reticulum (ER) and Golgi membranes. Localization of Sac1 responds to changes in glucose levels, yet the upstream signaling pathways that regulate Sac1 traffic are unknown. Here, we report that mitogen-activated protein kinase (MAPK) Hog1 transmits glucose signals to the Golgi and regulates localization of Sac1. We find that Hog1 is rapidly activated by both glucose starvation and glucose stimulation, which is independent of the well-characterized response to osmotic stress but requires the upstream element Ssk1 and is controlled by Snf1, the yeast homolog of AMP-activated kinase (AMPK). Elimination of either Hog1 or Snf1 slows glucose-induced translocation of Sac1 lipid phosphatase from the Golgi to the ER and thus delays PI(4)P accumulation at the Golgi. We conclude that a novel cross-talk between the HOG pathway and Snf1/AMPK is required for the metabolic control of lipid signaling at the Golgi.
authors.affiliation: Division of Nephrology & Hypertension, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Hailan
authors.initials: H
authors.lastname: Piao
authors.forename: John
authors.initials: J
authors.lastname: MacLean Freed
authors.forename: Peter
authors.initials: P
authors.lastname: Mayinger
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018129:Phosphatidylinositol Phosphates; C087199:SSK1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C037178:phosphatidylinositol 4-phosphate; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C081864:SAC1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose