title: Sphingolipids regulate the yeast high-osmolarity glycerol response pathway.
abstract: The yeast high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase pathway is activated in response to hyperosmotic stress via two independent osmosensing branches, the Sln1 branch and the Sho1 branch. While the mechanism by which the osmosensing machinery activates the downstream MAP kinase cascade has been well studied, the mechanism by which the machinery senses and responds to hyperosmotic stress remains to be clarified. Here we report that inhibition of the de novo sphingolipid synthesis pathway results in activation of the HOG pathway via both branches. Inhibition of ergosterol biosynthesis also induces activation of the HOG pathway. Sphingolipids and sterols are known to be tightly packed together in cell membranes to form partitioned domains called rafts. Raft-enriched detergent-resistant membranes (DRMs) contain both Sln1 and Sho1, and sphingolipid depletion and hyperosmotic stress have similar effects on the osmosensing machinery of the HOG pathway: dissociation of an Sln1-containing protein complex and elevated association of Sho1 with DRMs. These observations reveal the sphingolipid-mediated regulation of the osmosensing machinery of the HOG pathway.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Mirai
authors.initials: M
authors.lastname: Tanigawa
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
authors.forename: Minoru
authors.initials: M
authors.lastname: Terashima
authors.forename: Terunao
authors.initials: T
authors.lastname: Takahara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maeda
mesh_terms: D005372:Filipin / Q000494:pharmacology; D005800:Genes, Fungal; D005990:Glycerol / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C459787:SHO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D005372:Filipin; D011494:Protein Kinases; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C083749:SLN1 protein, S cerevisiae; D005990:Glycerol