Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function.
Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function.
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DOI：
10.1083/jcb.200401157
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发表时间：
2004-08-02
影响因子：
7.8
通讯作者：
Eide, David J
中科院分区：
文献类型：
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作者：
Ellis, Charissa D;Wang, Fudi;MacDiarmid, Colin W;Clark, Suzanne;Lyons, Thomas;Eide, David J
在本报告中，我们表明锌是酿酒酵母内质网功能所必需的。这种酵母中缺锌会诱导未折叠蛋白反应 (UPR)，这是一种通常由未折叠内质网蛋白激活的系统。 Msc2 是金属离子转运蛋白阳离子扩散促进剂 (CDF) 家族的成员，之前被认为与锌稳态有关。我们的结果表明，Msc2 是锌进入内质网的一种途径。当 Msc2 以正常水平表达时，定位于 ER。 MSC2 突变体中，低锌条件下的 UPR 诱导会加剧。遗传和生化证据表明，这种 UPR 诱导是由于真正的 ER 功能障碍。值得注意的是，我们发现 ER 相关蛋白降解在锌限制的 msc2 突变体中存在缺陷。我们还表明，液泡 CDF 蛋白 Zrc1 和 Cot1 是 ER 锌获取的其他途径。最后，缺锌会上调哺乳动物的内质网应激反应，表明真核生物的内质网功能对锌的需求是保守的。
In this report, we show that zinc is required for endoplasmic reticulum function in Saccharomyces cerevisiae. Zinc deficiency in this yeast induces the unfolded protein response (UPR), a system normally activated by unfolded ER proteins. Msc2, a member of the cation diffusion facilitator (CDF) family of metal ion transporters, was previously implicated in zinc homeostasis. Our results indicate that Msc2 is one route of zinc entry into the ER. Msc2 localizes to the ER when expressed at normal levels. UPR induction in low zinc is exacerbated in an msc2 mutant. Genetic and biochemical evidence indicates that this UPR induction is due to genuine ER dysfunction. Notably, we found that ER-associated protein degradation is defective in zinc-limited msc2 mutants. We also show that the vacuolar CDF proteins Zrc1 and Cot1 are other pathways of ER zinc acquisition. Finally, zinc deficiency up-regulates the mammalian ER stress response indicating a conserved requirement for zinc in ER function among eukaryotes.