Tail-anchored (TA) proteins fulfill diverse cellular functions within different organellar membranes. Their characteristic C-terminal transmembrane segment renders TA proteins inherently prone to aggregation and necessitates their posttranslational targeting. The guided entry of TA proteins (GET in yeast)/transmembrane recognition complex (TRC in humans) pathway represents a major route for TA proteins to the endoplasmic reticulum (ER). Here, we review important new insights into the capture of nascent TA proteins at the ribosome by the GET pathway pretargeting complex and the mechanism of their delivery into the ER membrane by the GET receptor insertase. Interestingly, several alternative routes by which TA proteins can be targeted to the ER have emerged, raising intriguing questions about how selectivity is achieved during TA protein capture. Furthermore, mistargeting of TA proteins is a fundamental cellular problem, and we discuss the recently discovered quality control machineries in the ER and outer mitochondrial membrane for displacing mislocalized TA proteins.

中文翻译：

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尾部锚定蛋白的捕获和递送至内质网

尾锚定 (TA) 蛋白在不同的细胞器膜内实现不同的细胞功能。它们特有的 C 端跨膜片段使 TA 蛋白本质上易于聚集，并且需要它们的翻译后靶向。TA 蛋白（酵母中的 GET）/跨膜识别复合物（人类中的 TRC）途径的引导进入代表了 TA 蛋白进入内质网 (ER) 的主要途径。在这里，我们回顾了关于 GET 途径预靶向复合物在核糖体上捕获新生 TA 蛋白以及通过 GET 受体插入酶将其递送到 ER 膜的机制的重要新见解。有趣的是，已经出现了几种将 TA 蛋白靶向 ER 的替代途径，这引发了关于在 TA 蛋白捕获过程中如何实现选择性的有趣问题。此外，TA 蛋白的错误定位是一个基本的细胞问题，我们讨论了最近在 ER 和线粒体外膜中发现的用于取代错误定位的 TA 蛋白的质量控制机制。