Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p in the apparent absence of endocytosis
Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p in the apparent absence of endocytosis
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DOI：
10.1002/j.1460-2075.1996.tb00720.x
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发表时间：
1996-07-15
期刊：
影响因子：
11.4
通讯作者：
Klausner, RD
中科院分区：
文献类型：
--
作者：
Ooi, CE;Rabinovich, E;Klausner, RD
细胞表面蛋白库需要根据细胞外环境的变化进行调节。在这项研究中，我们研究了酿酒酵母质膜铜转运蛋白 Ctr1p 的蛋白质周转，以响应细胞外铜水平的变化。由于 Ctr1p 介导细胞对铜的高亲和力摄取，因此其表达的调节预计会参与铜的稳态。我们证明，当细胞在低浓度铜中生长时，Ctr1p 是一种稳定的蛋白质，但细胞暴露于高浓度铜（10 μM）会引发细胞表面 Ctr1p 的降解。这种降解似乎是 Ctr1p 特有的，并且在测试的另一种酵母质膜蛋白中不会发生。当细胞接触铜时，可以看到一些 Ctr1p 的内化。然而，内吞作用（end3、end4和chc1-ts）和液泡降解（pep4）缺陷的酵母突变株表现出铜依赖性Ctr1p降解，表明内化和递送至液泡并不是导致降解的主要机制。此外，胞浆尾部缺失的 Ctr1p 变体在细胞接触铜时不会内化，但仍会被降解。这些观察结果表明，质膜上的蛋白水解很可能解释了 Ctr1p 的铜依赖性周转，并表明酵母中存在一种新的质膜蛋白周转途径。
The cell surface protein repertoire needs to be regulated in response to changes in the extracellular environment. In this study, we investigate protein turnover of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p, in response to a change in extracellular copper levels. As Ctr1p mediates high affinity uptake of copper into the cell, modulation of its expression is expected to be involved in copper homeostasis. We demonstrate that Ctr1p is a stable protein when cells are grown in low concentrations of copper, but that exposure of cells to high concentrations of copper (10 mu M) triggers degradation of cell surface Ctr1p. This degradation appears to be specific for Ctr1p and does not occur with another yeast plasma membrane protein tested. Internalization of some Ctr1p can be seen when cells are exposed to copper. However, yeast mutant strains defective in endocytosis (end3, end4 and chc1-ts) and vacuolar degradation (pep4) exhibit copper-dependent Ctr1p degradation, indicating that internalization and delivery to the vacuole is not the principal mechanism responsible for degradation. In addition, a variant Ctr1p with a deletion in the cytosolic tail is not internalized upon exposure of cells to copper, but is nevertheless degraded. These observations indicate that proteolysis at the plasma membrane most likely explains copper-dependent turnover of Ctr1p and point to the existence of a novel pathway in yeast for plasma membrane protein turnover.