title: The β-arrestin-like protein Rim8 is hyperphosphorylated and complexes with Rim21 and Rim101 to promote adaptation to neutral-alkaline pH.
abstract: β-Arrestin proteins are critical for G-protein-coupled receptor desensitization and turnover. However, β-arrestins have recently been shown to play direct roles in nonheterotrimeric G-protein signal transduction. The Candida albicans β-arrestin-like protein Rim8 is required for activation of the Rim101 pH-sensing pathway and for pathogenesis. We have found that C. albicans Rim8 is posttranslationally modified by phosphorylation and specific phosphorylation states are associated with activation of the pH-sensing pathway. Rim8 associated with both the receptor Rim21 and the transcription factor Rim101, suggesting that Rim8 bridges the signaling and activation steps of the pathway. Finally, upon activation of the Rim101 transcription factor, C. albicans Rim8 was transcriptionally repressed and Rim8 protein levels were rapidly reduced. Our studies suggest that Rim8 is taken up into multivesicular bodies and degraded within the vacuole. In total, our results reveal a novel mechanism for tightly regulating the activity of a signal transduction pathway. Although the role of β-arrestin proteins in mammalian signal transduction pathways has been demonstrated, relatively little is known about how β-arrestins contribute to signal transduction. Our analyses provide some insights into potential roles.
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gomez-Raja
authors.forename: Dana A
authors.initials: DA
authors.lastname: Davis
mesh_terms: D000222:Adaptation, Physiological; D000468:Alkalies / Q000737:chemistry; D015153:Blotting, Western; D002176:Candida albicans / Q000737:chemistry* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D059748:Proteolysis; D011956:Receptors, Cell Surface / Q000737:chemistry; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic; D014617:Vacuoles / Q000737:chemistry / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics
chemical_list: D000468:Alkalies; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; C489602:RIM101 protein, Candida albicans; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D037521:Virulence Factors; C539750:VPS4 protein, Candida albicans