A transporter in the endoplasmic reticulum of Schizosaccharomyces pombe cells mediates zinc storage and differentially affects transition metal tolerance
A transporter in the endoplasmic reticulum of Schizosaccharomyces pombe cells mediates zinc storage and differentially affects transition metal tolerance
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DOI：
10.1074/jbc.m201031200
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发表时间：
2002-05-17
影响因子：
4.8
通讯作者：
zur Nieden, U
中科院分区：
文献类型：
--
作者：
Clemens, S;Bloss, T;zur Nieden, U
阳离子扩散促进剂（CDF）家族代表一类普遍存在的金属转运体。在粟酒裂殖酵母中的CDF的失活，导致对各种金属的耐受性的显著不同的影响。一个缺失突变体是Zn ~（2+）/Co ~（2+）超敏感的，但表现出显著增强的Cd ~（2+）和Ni ~（2+）耐受性。突变细胞中锌、钴和镉的积累减少。非空泡锌含量，通过分析电子显微镜测量，是较低的zhf（-）细胞与野生型细胞相比，在存在升高的Zn 2+浓度。对镉毒性的保护作用是独立的植物螯合解毒途径。当zhf被破坏时，植物螯合素脱氢酶缺陷细胞表现出极强的（约200倍）镉耐受性。免疫金标记显示Zhf的内质网（ER）定位。电子光谱成像显示，锌的积累与Zhf定位相一致，证明了ER在金属储存和Zhf参与细胞锌稳态中的重要作用。此外，这些观察结果表明，镉离子发挥其毒性作用的细胞代谢中的ER，而不是在胞质溶胶。
The cation diffusion facilitator (CDF) family represents a class of ubiquitous metal transporters. Inactivation of a CDF in Schizosaccharomyces pombe, Zhf, causes drastically different effects on the tolerance toward various metals. A deletion mutant is Zn2+/Co2+-hypersensitive yet displays significantly enhanced Cd2+ and Ni2+ tolerance. Accumulation of zinc, cobalt, and cadmium is reduced in mutant cells. Non-vacuolar zinc content, as measured by analytical electron microscopy, is lower in zhf(-) cells compared with wild-type cells in the presence of elevated Zn2+ concentrations. The protective effect against cadmium toxicity is independent of the phytochelatin detoxification pathway. Phytochelatin synthase-deficient cells show extremely enhanced (about 200-fold) cadmium tolerance when zhf is disrupted. Immunogold labeling indicates endoplasmic reticulum (ER) localization of Zhf. Electron spectroscopic imaging shows that accumulation of zinc coincides with Zhf localization, demonstrating a major role of the ER for metal storage and the involvement of Zhf in cellular zinc homeostasis. Also, these observations indicate that Cd2+ ions exert their toxic effects on cellular metabolism in the ER rather than in the cytosol.