Gallon Matthew, Cullen Peter J
*The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, U.K.
Biochem Soc Trans. 2015 Feb;43(1):33-47. doi: 10.1042/BST20140290.
The evolutionarily conserved endosomal retromer complex rescues transmembrane proteins from the lysosomal degradative pathway and facilitates their recycling to other cellular compartments. Retromer functions in conjunction with numerous associated proteins, including select members of the sorting nexin (SNX) family. In the present article, we review the molecular architecture and cellular roles of retromer and its various functional partners. The endosomal network is a crucial hub in the trafficking of proteins through the cellular endomembrane system. Transmembrane proteins, here termed cargos, enter endosomes by endocytosis from the plasma membrane or by trafficking from the trans-Golgi network (TGN). Endosomal cargo proteins face one of the two fates: retention in the endosome, leading ultimately to lysosomal degradation or export from the endosome for reuse ('recycling'). The balance of protein degradation and recycling is crucial to cellular homoeostasis; inappropriate sorting of proteins to either fate leads to cellular dysfunction. Retromer is an endosome-membrane-associated protein complex central to the recycling of many cargo proteins from endosomes, both to the TGN and the plasma membrane (and other specialized compartments, e.g. lysosome-related organelles). Retromer function is reliant on a number of proteins from the SNX family. In the present article, we discuss this inter-relationship and how defects in retromer function are increasingly being linked with human disease.
进化上保守的内体逆向转运复合物可将跨膜蛋白从溶酶体降解途径中拯救出来，并促进其循环至其他细胞区室。逆向转运复合物与众多相关蛋白协同发挥作用，包括分选连接蛋白（SNX）家族的某些成员。在本文中，我们综述了逆向转运复合物及其各种功能伙伴的分子结构和细胞作用。内体网络是蛋白质通过细胞内膜系统进行运输的关键枢纽。跨膜蛋白（此处称为货物）通过从质膜的内吞作用或从反式高尔基体网络（TGN）的运输进入内体。内体货物蛋白面临两种命运之一：保留在内体中，最终导致溶酶体降解，或从内体输出以供再利用（“循环利用”）。蛋白质降解和循环利用的平衡对细胞稳态至关重要；蛋白质错误分选至任何一种命运都会导致细胞功能障碍。逆向转运复合物是一种与内体膜相关的蛋白复合物，对于许多货物蛋白从内体循环至TGN和质膜（以及其他特殊区室，如溶酶体相关细胞器）至关重要。逆向转运复合物的功能依赖于SNX家族的多种蛋白。在本文中，我们讨论了这种相互关系以及逆向转运复合物功能缺陷如何越来越多地与人类疾病相关联。
