title: A phenomics approach in yeast links proton and calcium pump function in the Golgi.
abstract: The Golgi-localized Ca2+- and Mn2+-transporting ATPase Pmr1 is important for secretory pathway functions. Yeast mutants lacking Pmr1 show growth sensitivity to multiple drugs (amiodarone, wortmannin, sulfometuron methyl, and tunicamycin) and ions (Mn2+ and Ca2+). To find components that function within the same or parallel cellular pathways as Pmr1, we identified genes that shared multiple pmr1 phenotypes. These genes were enriched in functional categories of cellular transport and interaction with cellular environment, and predominantly localize to the endomembrane system. The vacuolar-type H+-transporting ATPase (V-ATPase), rather than other Ca2+ transporters, was found to most closely phenocopy pmr1Delta, including a shared sensitivity to Zn2+ and calcofluor white. However, we show that pmr1Delta mutants maintain normal vacuolar and prevacuolar pH and that the two transporters do not directly influence each other's activity. Together with a synthetic fitness defect of pmr1DeltavmaDelta double mutants, this suggests that Pmr1 and V-ATPase work in parallel toward a common function. Overlaying data sets of growth sensitivities with functional screens (carboxypeptidase secretion and Alcian Blue binding) revealed a common set of genes relating to Golgi function. We conclude that overlapping phenotypes with Pmr1 reveal Golgi-localized functions of the V-ATPase and emphasize the importance of calcium and proton transport in secretory/prevacuolar traffic.
authors.affiliation: Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Yadav
authors.forename: Sabina
authors.initials: S
authors.lastname: Muend
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rajini
authors.initials: R
authors.lastname: Rao
mesh_terms: D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D025141:Drug Resistance, Fungal / Q000235:genetics; D016681:Genome, Fungal; D006056:Golgi Apparatus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C447616:VMA5 protein, S cerevisiae; D025262:Vacuolar Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium