Integral membrane proteins of the cell surface and most intracellular compartments of eukaryotic cells are assembled at the endoplasmic reticulum. Two highly conserved and parallel pathways mediate membrane protein targeting to and insertion into this organelle. The classical cotranslational pathway, utilized by most membrane proteins, involves targeting by the signal recognition particle followed by insertion via the Sec61 translocon. A more specialized posttranslational pathway, employed by many tail-anchored membrane proteins, is composed of entirely different factors centered around a cytosolic ATPase termed TRC40 or Get3. Both of these pathways overcome the same biophysical challenges of ferrying hydrophobic cargo through an aqueous milieu, selectively delivering it to one among several intracellular membranes and asymmetrically integrating its transmembrane domain(s) into the lipid bilayer. Here, we review the conceptual and mechanistic themes underlying these core membrane protein insertion pathways, the complexities that challenge our understanding, and future directions to overcome these obstacles.

中文翻译：

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膜蛋白插入内质网。

细胞表面的完整膜蛋白和真核细胞的大多数细胞内隔室在内质网中组装。两个高度保守和平行的途径介导膜蛋白靶向并插入到该细胞器中。大多数膜蛋白使用的经典共翻译途径涉及通过信号识别粒子进行靶向，然后通过 Sec61 转位子插入。许多尾锚定膜蛋白采用的一种更特殊的翻译后途径由完全不同的因子组成，这些因子以称为 TRC40 或 Get3 的胞质 ATP 酶为中心。这两种途径都克服了通过水环境运送疏水性货物的相同生物物理挑战，选择性地将其输送到几个细胞内膜之一，并将其​​跨膜结构域不对称地整合到脂质双层中。在这里，我们回顾了这些核心膜蛋白插入途径背后的概念和机制主题、挑战我们理解的复杂性以及克服这些障碍的未来方向。