Pmr1, a Golgi Ca2+/Mn2+-ATPase, is a regulator of the target of rapamycin (TOR) signaling pathway in yeast

Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17840-5. doi: 10.1073/pnas.0604303103. Epub 2006 Nov 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Antifungal Agents / metabolism
  • Calcium-Transporting ATPases / genetics
  • Calcium-Transporting ATPases / metabolism*
  • Epistasis, Genetic
  • Gene Expression Regulation, Fungal
  • Golgi Apparatus / enzymology*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae* / cytology
  • Saccharomyces cerevisiae* / enzymology
  • Signal Transduction / physiology*
  • Sirolimus / metabolism
  • Transcription Factors / metabolism

Substances

  • Amino Acid Transport Systems
  • Antifungal Agents
  • GAP1 protein, S cerevisiae
  • Molecular Chaperones
  • Recombinant Fusion Proteins
  • SSC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • NPR1 protein, S cerevisiae
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae
  • Calcium-Transporting ATPases
  • Sirolimus