title: MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators.
abstract: The aquaglyceroprin Fps1 is responsible for glycerol transport in yeast in response to changes in extracellular osmolarity. Control of Fps1 channel activity in response to hyperosmotic shock involves a redundant pair of regulators, Rgc1 (regulator of the glycerol channel 1) and Rgc2, and the MAPK Hog1 (high-osmolarity glycerol response 1). However, the mechanism by which these factors influence channel activity is unknown. We show that Rgc2 maintains Fps1 in the open channel state in the absence of osmotic stress by binding to its C-terminal cytoplasmic domain. This interaction involves a tripartite pleckstrin homology (PH) domain within Rgc2 and a partial PH domain within Fps1. Activation of Hog1 in response to hyperosmotic shock induces the rapid eviction of Rgc2 from Fps1 and consequent channel closure. Hog1 was recruited to the N-terminal cytoplasmic domain of Fps1, which it uses as a platform from which to multiply phosphorylate Rgc2. Thus, these results reveal the mechanism by which Hog1 regulates Fps1 in response to hyperosmotic shock.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118, USA;
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reiter
authors.forename: Ilse
authors.initials: I
authors.lastname: Dohnal
authors.forename: Christa
authors.initials: C
authors.lastname: Gregori
authors.forename: Sara
authors.initials: S
authors.lastname: Beese-Sims
authors.forename: Karl
authors.initials: K
authors.lastname: Kuchler
authors.forename: Gustav
authors.initials: G
authors.lastname: Ammerer
authors.forename: David E
authors.initials: DE
authors.lastname: Levin
mesh_terms: D008565:Membrane Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009997:Osmotic Pressure / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C093263:FPS1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases
keywords: Fps1; Hog1; Rgc1; Rgc2; osmotic shock; phosphoproteomics