title: The Rim101 pathway is involved in Rsb1 expression induced by altered lipid asymmetry.
abstract: Biological membranes consist of lipid bilayers. The lipid compositions between the two leaflets of the plasma membrane differ, generating lipid asymmetry. Maintenance of proper lipid asymmetry is physiologically quite important, and its collapse induces several cellular responses including apoptosis and platelet coagulation. Thus, a change in lipid asymmetry must be restored to maintain "lipid asymmetry homeostasis." However, to date no lipid asymmetry-sensing proteins or any related downstream signaling pathways have been identified. We recently demonstrated that expression of the putative yeast sphingoid long-chain base transporter/translocase Rsb1 is induced when glycerophospholipid asymmetry is altered. Using mutant screening, we determined that the pH-responsive Rim101 pathway, the protein kinase Mck1, and the transcription factor Mot3 all act in lipid asymmetry signaling, and that the Rim101 pathway was activated in response to a change in lipid asymmetry. The activated transcription factor Rim101 induces Rsb1 expression via repression of another transcription repressor, Nrg1. Changes in lipid asymmetry are accompanied by cell surface exposure of negatively charged phospholipids; we speculate that the Rim101 pathway recognizes the surface charges.
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ikeda
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
authors.forename: Aki
authors.initials: A
authors.lastname: Denpoh
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D050505:Mutant Proteins / Q000302:isolation & purification / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010714:Phosphatidylethanolamines / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D050505:Mutant Proteins; D010714:Phosphatidylethanolamines; C489601:RIM101 protein, S cerevisiae; C465340:RSB1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins