Quality control of nonstop membrane proteins at the ER membrane and in the cytosol.
Quality control of nonstop membrane proteins at the ER membrane and in the cytosol.
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DOI：
10.1038/srep30795
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发表时间：
2016-08-02
影响因子：
4.6
通讯作者：
Endo T
中科院分区：
文献类型：
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作者：
Arakawa S;Yunoki K;Izawa T;Tamura Y;Nishikawa S;Endo T
由于针对细胞器靶向蛋白质的无终止密码子的信使RNA（无终止mRNA）及其翻译产物（无终止蛋白质）会产生堵塞的易位子通道以及停滞的核糖体，细胞具有降解无终止mRNA和无终止蛋白质以及通过将无终止蛋白质释放到细胞器腔中来清理易位子（例如Sec61复合物）的机制。在此，我们追踪了酵母中具有不同膜拓扑结构的无终止内质网（ER）膜蛋白的命运，以评估依赖于Ltn1的胞质降解以及依赖于Dom34的无终止膜蛋白释放的重要性。对于具有不同拓扑结构的膜蛋白，依赖于Ltn1的降解有所不同，并且其失效并不影响内质网蛋白质输入或细胞生长。另一方面，从核糖体释放新生多肽的依赖于Dom34的过程失败会导致Sec61通道堵塞，进而抑制其他蛋白质输入内质网，从而导致细胞生长缺陷。因此，从翻译装置释放新生链在清理堵塞的内质网易位子通道以及维持正常细胞功能方面更为重要。
Since messenger RNAs without a stop codon (nonstop mRNAs) for organelle-targeted proteins and their translation products (nonstop proteins) generate clogged translocon channels as well as stalled ribosomes, cells have mechanisms to degrade nonstop mRNAs and nonstop proteins and to clear the translocons (e.g. the Sec61 complex) by release of nonstop proteins into the organellar lumen. Here we followed the fate of nonstop endoplasmic reticulum (ER) membrane proteins with different membrane topologies in yeast to evaluate the importance of the Ltn1-dependent cytosolic degradation and the Dom34-dependent release of the nonstop membrane proteins. Ltn1-dependent degradation differed for membrane proteins with different topologies and its failure did not affect ER protein import or cell growth. On the other hand, failure in the Dom34-dependent release of the nascent polypeptide from the ribosome led to the block of the Sec61 channel and resultant inhibition of other protein import into the ER caused cell growth defects. Therefore, the nascent chain release from the translation apparatus is more instrumental in clearance of the clogged ER translocon channel and thus maintenance of normal cellular functions.