title: Rgc2 Regulator of Glycerol Channel Fps1 Functions as a Homo- and Heterodimer with Rgc1.
abstract: The plasma membrane aquaglyceroporin Fps1 is responsible for glycerol transport in yeast in response to changes in extracellular osmolarity. Fps1 functions as a homotetramer, and control of its channel activity in response to hyperosmotic shock involves a redundant pair of fungus-specific regulators, Rgc1 and Rgc2 (regulators of the glycerol channel), and the mitogen-activatd protein kinase (MAPK) Hog1 (high-osmolarity glycerol response). Rgc1 and Rgc2 maintain Fps1 in an open-channel state by binding to its C-terminal cytoplasmic domain. Phosphorylation of Rgc1 and Rgc2 by Hog1 induces their eviction from Fps1 and consequent channel closure. In the absence of Fps1 channel function, cells experience chronic cell wall stress, which may be exploited for antifungal drug development. We show here that Rgc1 and Rgc2 form homodimers and heterodimers with each other and that dimer formation of Rgc2 is mediated by its N-terminal domain. Mutations that prevent Rgc2 dimerization block its ability to open Fps1. Therefore, the Rgc-Rgc dimer interface might be an attractive drug target.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA delevin@bu.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Levin
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009994:Osmolar Concentration; D010766:Phosphorylation; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C093263:FPS1 protein, S cerevisiae; D008565:Membrane Proteins; C548444:Rgc1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D005990:Glycerol