Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation
Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation
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DOI：
10.1093/emboj/16.15.4540
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发表时间：
1997-08-01
期刊：
影响因子：
11.4
通讯作者：
Romisch, K
中科院分区：
文献类型：
--
作者：
Pilon, M;Schekman, R;Romisch, K
长期以来，错误折叠的分泌蛋白的降解一直被认为发生在内质网（ER）的内腔。然而，最近的证据表明，这样的蛋白质，而不是降解的蛋白酶体在胞质溶胶中，虽然目前还不清楚蛋白质是如何被运出的ER，在这里，我们提供了第一个遗传证据，Sec61 p，孔形成亚基的蛋白质转运通道在ER膜，是直接参与出口的错误折叠分泌蛋白。我们描述了两个新的酵母Sec61p突变体，它们在完整的酵母细胞和无细胞系统中对输入到ER是冷敏感的，来自这些突变体的微粒体在输出错误折叠的分泌蛋白方面是缺陷的，这些蛋白被困在ER中并与Sec61p相关，我们得出结论，错误折叠的分泌蛋白出口的降解从ER到胞质溶胶通过Sec61p形成的通道。
Degradation of misfolded secretory proteins has long been assumed to occur in the lumen of the endoplasmic reticulum (ER). Recent evidence, however, suggests that such proteins are instead degraded by proteasomes in the cytosol, although it remains unclear how the proteins are transported out of the ER, Here we provide the first genetic evidence that Sec61p, the pore-forming subunit of the protein translocation channel in the ER membrane, is directly involved in the export of misfolded secretory proteins. We describe two novel mutants in yeast Sec61p that are cold-sensitive for import into the ER in both intact yeast cells and a cell-free system, Microsomes derived from these mutants are defective in exporting misfolded secretory proteins, These proteins become trapped in the ER and are associated with Sec61p, We conclude that misfolded secretory proteins are exported for degradation from the ER to the cytosol via channels formed by Sec61p.