Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast Saccharomyces cerevisiae.
The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated second-site suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16delta deletion strain, and a cdc1delta cos16delta double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.
Paidhungat
M
M
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Garrett
S
S
D020727:ADP-Ribosylation Factors; D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D005800:Genes, Fungal; D016153:Genes, Suppressor; D006706:Homeostasis / Q000502:physiology*; D008345:Manganese / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D013347:Subcellular Fractions; D013696:Temperature; D014617:Vacuoles; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; C090459:CDC1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D008565:Membrane Proteins; C071657:PEP3 protein, S cerevisiae; C065710:PEP5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C080045:VPS16 protein, S cerevisiae; C107528:VPS4 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D008345:Manganese; D002268:Carboxypeptidases; D043402:Cathepsin A; D016282:Aspartic Acid Endopeptidases; C022442:aspergillopepsin II; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors