title: The C-terminal Cytosolic Region of Rim21 Senses Alterations in Plasma Membrane Lipid Composition: INSIGHTS INTO SENSING MECHANISMS FOR PLASMA MEMBRANE LIPID ASYMMETRY.
abstract: Yeast responds to alterations in plasma membrane lipid asymmetry and external alkalization via the sensor protein Rim21 in the Rim101 pathway. However, the sensing mechanism used by Rim21 remains unclear. Here, we found that the C-terminal cytosolic domain of Rim21 (Rim21C) fused with GFP was associated with the plasma membrane under normal conditions but dissociated upon alterations in lipid asymmetry or external alkalization. This indicates that Rim21C contains a sensor motif. Rim21C contains multiple clusters of charged residues. Among them, three consecutive Glu residues (EEE motif) were essential for Rim21 function and dissociation of Rim21C from the plasma membrane in response to changes in lipid asymmetry. In contrast, positively charged residues adjacent to the EEE motif were required for Rim21C to associate with the membrane. We therefore propose an "antenna hypothesis," in which Rim21C moves to or from the plasma membrane and functions as the sensing mechanism of Rim21.
authors.affiliation: From the Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nishino
authors.affiliation: From the Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Obara
authors.affiliation: From the Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan kihara@pharm.hokudai.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008055:Lipids; D011956:Receptors, Cell Surface; C547025:Rim21 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: Rim21; alkaline response; lipid asymmetry; lipid bilayer; phospholipid; plasma membrane; signal transduction; yeast