Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast
Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast
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DOI：
10.1091/mbc.e07-08-0805
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发表时间：
2008-04-01
影响因子：
3.3
通讯作者：
Kuno, Takayoshi
中科院分区：
文献类型：
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作者：
Fang, Yue;Sugiura, Reiko;Kuno, Takayoshi
我们筛选了对钙调磷酸酶抑制剂FK506和高浓度MgCl2敏感的突变，并分离出cis4-1突变体，该突变体是编码阳离子扩散促进剂（CDF）蛋白的基因等位基因，该基因在结构上与锌转运蛋白相关。与此一致的是，细胞外Zn2+的添加抑制了cis4突变细胞的表型。cis4突变体和另一个cdf编码基因SPBC16E9.14c（我们命名为zrg(17+)）的突变细胞具有共同的和非加性的锌抑制表型，cis4和Zrg17物理相互作用。Cis4定位于顺式高尔基体，表明Cis4负责将Zn2+摄取到顺式高尔基体。cis4突变细胞表现出细胞壁薄弱和酸性磷酸酶分泌减少等表型，这些表型被认为是由于膜运输受损造成的。此外，cis4缺失细胞在ypt3-i5、ryh1-i6、gdi1-i11和apm1-1这四种膜转运突变体中均表现出合成生长缺陷。有趣的是，细胞外添加Zn2+显著抑制了ypt3-i5和apm1-1突变细胞的表型。这些结果表明Cis4与Zrg17形成异质功能复合物，Cis4通过调节裂变酵母的锌稳态参与高尔基膜运输。
We screened for mutations that confer sensitivities to the calcineurin inhibitor FK506 and to a high concentration of MgCl2 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 Zn2+ suppressed the phenotypes of the cis4 mutant cells. The cis4 mutants and the mutant cells of another CDF-encoding gene SPBC16E9.14c ( we named zrg(17+)) 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 Zn2+ 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 Zn2+ 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.