YKE4 (YIL023C) encodes a bidirectional zinc transporter in the endoplasmic reticulum of Saccharomyces cerevisiae
YKE4 (YIL023C) encodes a bidirectional zinc transporter in the endoplasmic reticulum of Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m604730200
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发表时间：
2006-08-11
影响因子：
4.8
通讯作者：
Kaplan, Jerry
中科院分区：
文献类型：
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作者：
Kumanovics, Attila;Poruk, Katherine E.;Kaplan, Jerry
YIL023C编码SLC39A或ZIP家族的一个成员，我们称其为酵母KE4(YKE4)，以其小鼠的同源基因命名。用Yke4p特异性抗血清将Yke4p定位于内质网(ER)膜。YKE4不是必需的基因；然而，YKE4的缺失导致对钙氟白色敏感，并在36摄氏度下在含高锌的呼吸底物上生长不良。过渡金属转运蛋白Zrc1p和Cot1p或小鼠同源基因mKe4在Delta yke4中的过表达抑制了呼吸底物上36℃的不良生长。我们发现Yke4p的作用取决于细胞的锌状态。在锌充足的环境中，Yke4p将锌运输到分泌途径中，YKE4的缺失导致锌抑制的细胞壁缺陷。在高锌条件下，锌通过Yke4p进入分泌途径是从胞浆中清除锌的一种方式，而YKE4的缺失导致有毒的锌在胞浆中积累。然而，在低胞质锌的条件下，Yke4p从分泌途径中移除锌，YKE4的缺失部分补偿了内质网锌导入蛋白Msc2p的丢失，因此有助于缓解内质网应激。在我们的模型中，Yke4p平衡了胞浆和分泌途径之间的锌水平，而之前描述的Msc2p-Zrg17p ER锌进口复合体的功能主要是在锌缺乏的条件下，以确保随时供应内质网功能所必需的锌，如磷脂生物合成和未折叠蛋白反应。
YIL023C encodes a member of the SLC39A, or ZIP, family, which we refer to as yeast KE4 (YKE4) after its mouse ortholog. Yke4p was localized to the endoplasmic reticulum (ER) membrane using Yke4p-specific antiserum. YKE4 is not an essential gene; however, deletion of YKE4 resulted in a sensitivity to calcofluor white and poor growth at 36 degrees C on respiratory substrates containing high zinc. Overexpression of transition metal transporters Zrc1p and Cot1p or the mouse orthologue mKe4 in Delta yke4 suppressed the poor growth at 36 degrees C on respiratory substrates. We found that the role of Yke4p depends on the zinc status of the cells. In a zinc-adequate environment, Yke4p transports zinc into the secretory pathway, and the deletion of YKE4 leads to a zinc-suppressible cell wall defect. In high zinc medium, transport of zinc into the secretory pathway through Yke4p is a way to eliminate zinc from the cytosol, and deletion of YKE4 leads to toxic zinc accumulation in the cytosol. Under low cytosolic zinc conditions, however, Yke4p removes zinc from the secretory pathway, and deletion of YKE4 partially compensates for the loss of Msc2p, an ER zinc importer, and therefore helps to alleviate ER stress. In our model, Yke4p balances zinc levels between the cytosol and the secretory pathway, whereas the previously described Msc2p-Zrg17p ER zinc importer complex functions mainly in zinc-depleted conditions to ensure a ready supply of zinc essential for ER functions, such as phospholipid biosynthesis and unfolded protein response.