title: Signaling events of the Rim101 pathway occur at the plasma membrane in a ubiquitination-dependent manner.
abstract: In yeast, external alkalization and alteration in plasma membrane lipid asymmetry are sensed by the Rim101 pathway. It is currently under debate whether the signal elicited by external alkalization is transduced to downstream molecules at the plasma membrane or via endocytosis of the Rim21 sensor protein at the late endosome. We found that the downstream molecules, including arrestin-related protein Rim8, calpain-like protein Rim13, and scaffold protein Rim20, accumulated at the plasma membrane upon external alkalization and that the accumulation was dependent on Rim21. Snf7, an endosomal sorting complex required for transport (ESCRT) III subunit also essential for the Rim101 pathway, localized to the plasma membrane, in addition to the late endosome, under alkaline conditions. Snf7 at the plasma membrane but not at the late endosome was shown to be involved in Rim101 signaling. In addition, the Rim101 pathway was normally activated, even when endocytosis was severely impaired. Considering this information as a whole, we propose that Rim101 signaling proceeds at the plasma membrane. We also found that activity of the Rsp5 ubiquitin ligase was required for recruiting the downstream molecules to the plasma membrane, suggesting that ubiquitination mediates Rim101 signaling at the plasma membrane.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Obara
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan kihara@pharm.hokudai.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
mesh_terms: D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism*; D057056:Cysteine Proteases / Q000235:genetics; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*; D054875:Ubiquitination / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; C489601:RIM101 protein, S cerevisiae; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C510979:Rim20 protein, S cerevisiae; C547025:Rim21 protein, S cerevisiae; C547024:Rim8 protein, S cerevisiae; C083890:SNF7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D057056:Cysteine Proteases; C578371:Rim13 protein, S cerevisiae; C469287:RSP5 protein, S cerevisiae