Department of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, MA 02138, USA.
Trends Biochem Sci. 2012 Oct;37(10):411-7. doi: 10.1016/j.tibs.2012.07.004. Epub 2012 Aug 30.
Many eukaryotic membrane proteins have a single C-terminal transmembrane domain that anchors them to a variety of organelles in secretory and endocytic pathways. These tail-anchored (TA) proteins are post-translationally inserted into the endoplasmic reticulum by molecular mechanisms that have long remained mysterious. This review describes how, in just the past 5 years, intense research by a handful of laboratories has led to identification of all the key components of one such mechanism, the guided entry of TA proteins (GET) pathway, which is conserved from yeast to man. The GET pathway is both surprisingly complicated and yet more experimentally tractable than most other membrane insertion mechanisms, and is rapidly revealing new fundamental concepts in membrane protein biogenesis.
许多真核膜蛋白都有一个单一的 C 末端跨膜结构域，该结构域将它们锚定在分泌和内吞途径中的各种细胞器上。这些尾部锚定（TA）蛋白通过长期以来一直神秘的分子机制被翻译后插入内质网。这篇综述描述了在过去的 5 年中，少数几个实验室的深入研究如何导致鉴定出一种这样的机制的所有关键成分，即 TA 蛋白的引导进入（GET）途径，该途径从酵母到人都是保守的。GET 途径不仅出人意料地复杂，而且比大多数其他膜插入机制更具实验可操作性，并且正在迅速揭示膜蛋白生物发生的新的基本概念。
