title: Pmr1, a Golgi Ca2+/Mn2+-ATPase, is a regulator of the target of rapamycin (TOR) signaling pathway in yeast.
abstract: The rapamycin.FKBP12 complex inhibits target of rapamycin (TOR) kinase in TORC1. We screened the yeast nonessential gene deletion collection to identify mutants that conferred rapamycin resistance, and we identified PMR1, encoding the Golgi Ca2+/Mn2+ -ATPase. Deleting PMR1 in two genetic backgrounds confers rapamycin resistance. Epistasis analyses show that Pmr1 functions upstream from Npr1 and Gln-3 in opposition to Lst8, a regulator of TOR. Npr1 kinase is largely cytoplasmic, and a portion localizes to the Golgi where amino acid permeases are modified and sorted. Nuclear translocation of Gln-3 and Gln-3 reporter activity in pmr1 cells are impaired, but expression of functional Gap1 in the plasma membrane of a pmr1 strain in response to nitrogen limitation is enhanced. These two phenotypes suggest up-regulation of Npr1 function in the absence of Pmr1. Together, our results establish that Pmr1-dependent Ca2+ and/or Mn2+ ion homeostasis is necessary for TOR signaling.
authors.affiliation: Departments of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Devasahayam
authors.forename: Danilo
authors.initials: D
authors.lastname: Ritz
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Helliwell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burke
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sturgill
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000201:enzymology*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D000935:Antifungal Agents; C491145:GAP1 protein, S cerevisiae; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C066958:NPR1 protein, S cerevisiae; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D000252:Calcium-Transporting ATPases; D020123:Sirolimus