Probing for membrane domains in the endoplasmic reticulum: retention and degradation of unassembled MHC class I molecules.
Probing for membrane domains in the endoplasmic reticulum: retention and degradation of unassembled MHC class I molecules.
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内质网膜域的探测：未组装的 MHC I 类分子的保留和降解。
DOI：
10.1091/mbc.01-07-0322
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Edidin,Michael
中科院分区：
文献类型：
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作者：
Spiliotis,EliasT;Pentcheva,Tsvetelina;Edidin,Michael
蛋白质生物合成的质量控制需要未组装/错误折叠分子的ER保留和ER相关降解（ERAD）。虽然存在一些证据表明ER组织为功能不同的膜结构域，但尚不清楚这些结构域是否参与未组装蛋白的保留和ERAD。在这里，它表明，未组装的MHC I类分子保留在ER中，而不在ER出口位点或β 2 m −/−细胞的ERGIC中积累。此外，这些分子没有聚集在ER膜上，即使当ERAD或它们与钙连接蛋白的结合被抑制时，它们也表现出高度移动的。然而，在ATP耗尽后，它们可逆地分离到ER膜结构域中，与ER出口位点不同，其包括钙连接蛋白和COPII，但不包括ERGIC标记蛋白p58。在蛋白酶体的长期抑制后也观察到该质量控制域。它的出现需要微管。分离的未折叠蛋白，ER-居民伴侣，和COPII可能是一个时间适应细胞应激。
Quality control of protein biosynthesis requires ER-retention and ER-associated degradation (ERAD) of unassembled/misfolded molecules. Although some evidence exists for the organization of the ER into functionally distinct membrane domains, it is unknown if such domains are involved in the retention and ERAD of unassembled proteins. Here, it is shown that unassembled MHC class I molecules are retained in the ER without accumulating at ER-exit sites or in the ERGIC of β2m−/−cells. Furthermore, these molecules did not cluster in the ER membrane and appeared to be highly mobile even when ERAD or their association with calnexin were inhibited. However, upon ATP depletion, they were reversibly segregated into an ER membrane domain, distinct from ER exit sites, which included calnexin and COPII, but not the ERGIC marker protein p58. This quality control domain was also observed upon prolonged inhibition of proteasomes. Microtubules were required for its appearance. Segregation of unfolded proteins, ER-resident chaperones, and COPII may be a temporal adaptation to cell stress.