ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration
ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration
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DOI：
10.1002/j.1460-2075.1996.tb00527.x
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发表时间：
1996-04-15
期刊：
影响因子：
11.4
通讯作者：
Findley, SD
中科院分区：
文献类型：
--
作者：
Palmiter, RD;Cole, TB;Findley, SD
通过与锌敏感的BHK细胞株互补，从大鼠肾脏cDNA表达文库中分离到编码第二锌转运蛋白（ZnT-2）的cDNA。从ZnT-2 cDNA的开放阅读框预测的蛋白质具有359个氨基酸，并以CTG密码子起始。它在整体拓扑结构上类似于ZnT-1（一种刺激锌外排的质膜蛋白），因为它有六个跨膜结构域，一个富含组氨酸的胞内环和一个长的C末端尾;然而，整体氨基酸同一性仅为26%。与ZnT-1不同，ZnT-1位于质膜中并通过刺激锌流出来降低细胞锌，ZnT-2位于囊泡上并允许锌敏感的BHK细胞将锌积累到比非转化细胞可耐受的水平高得多的水平。锌可视化这些囊泡与锌，锌特异性荧光探针。吖啶橙子或LysoTracker染色显示，蓄积锌的细胞内室呈酸性。表达ZnT-2的细胞长时间暴露于锌导致细胞内囊泡的增加。我们认为，ZnT-2保护这些细胞锌毒性，促进锌运输到内体/溶酶体室。
A cDNA encoding a second zinc transporter (ZnT-2) was isolated from a rat kidney cDNA expression library by complementation of a zinc-sensitive BHK cell line. The protein predicted from the open reading frame of ZnT-2 cDNA has 359 amino acids and initiates with a CTG codon. It resembles ZnT-1 (a plasma membrane protein that stimulates zinc efflux) in overall topology in that it has six membrane-spanning domains, a histidine-rich intracellular loop and a long C-terminal tail; however, the overall amino acid identity is only 26%. Unlike ZnT-1, which is in the plasma membrane and lowers cellular zinc by stimulating zinc efflux, ZnT-2 is localized on vesicles and allows the zinc-sensitive BHK cells to accumulate zinc to levels that are much higher than non-transformed cells can tolerate. Zinc was visualized within these vesicles with zinquin, a zinc-specific fluorescent probe. The intracellular compartment that accumulates zinc is acidic as revealed by staining with acridine orange or LysoTracker. Prolonged exposure of cells expressing ZnT-2 to zinc causes an accretion of intracellular vesicles. We suggest that ZnT-2 protects these cells from zinc toxicity by facilitating zinc transport into an endosomal/lysosomal compartment.