title: Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast.
abstract: We screened for mutations that confer sensitivities to the calcineurin inhibitor FK506 and to a high concentration of MgCl(2) and isolated the cis4-1 mutant, an allele of the gene encoding a cation diffusion facilitator (CDF) protein that is structurally related to zinc transporters. Consistently, the addition of extracellular Zn(2+) suppressed the phenotypes of the cis4 mutant cells. The cis4 mutants and the mutant cells of another CDF-encoding gene SPBC16E9.14c (we named zrg17(+)) shared common and nonadditive zinc-suppressible phenotypes, and Cis4 and Zrg17 physically interacted. Cis4 localized at the cis-Golgi, suggesting that Cis4 is responsible for Zn(2+) uptake to the cis-Golgi. The cis4 mutant cells showed phenotypes such as weak cell wall and decreased acid phosphatase secretion that are thought to be resulting from impaired membrane trafficking. In addition, the cis4 deletion cells showed synthetic growth defects with all the four membrane-trafficking mutants tested, namely ypt3-i5, ryh1-i6, gdi1-i11, and apm1-1. Interestingly, the addition of extracellular Zn(2+) significantly suppressed the phenotypes of the ypt3-i5 and apm1-1 mutant cells. These results suggest that Cis4 forms a heteromeric functional complex with Zrg17 and that Cis4 is implicated in Golgi membrane trafficking through the regulation of zinc homeostasis in fission yeast.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yada-Matsushima
authors.forename: Hirotatsu
authors.initials: H
authors.lastname: Umeno
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kuno
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D006056:Golgi Apparatus / Q000378:metabolism*; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; C577190:Cis4 protein, S pombe; D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; C017800:zinc-binding protein; D019703:Calcineurin; D000135:Acid Phosphatase; D015032:Zinc