Department of Pharmacology, Brain Korea21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Department of Pharmacology, Brain Korea21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Semin Cell Dev Biol. 2018 Nov;83:59-66. doi: 10.1016/j.semcdb.2018.03.016. Epub 2018 Mar 28.
Over the past 20 years it has become evident that eukaryotic cells utilize both conventional and unconventional pathways to deliver proteins to their target sites. Most proteins with a signal peptide and/or a transmembrane domain are conventionally transported through the endoplasmic reticulum to the Golgi apparatus and then to the plasma membrane. However, an increasing number of both soluble cargos (Type I, II, and III) and integral membrane proteins (Type IV) have been found to reach the plasma membrane via unconventional protein secretion (UPS) pathways that bypass the Golgi apparatus under certain conditions, such as cellular stress or development. Well-known examples of transmembrane proteins that undergo Type IV UPS pathways are position-specific antigen subunit alpha 1 integrin, cystic fibrosis transmembrane conductance regulator, myeloproliferative leukemia virus oncogene, and pendrin. Although we collectively refer to all Golgi-bypassing routes as UPS, individual trafficking pathways are diverse compared to the conventional pathways, and the molecular mechanisms of UPS pathways are not yet completely defined. This review summarizes the intracellular trafficking pathways of UPS cargo proteins, particularly those with transmembrane domains, and discusses the molecular machinery involved in the UPS of transmembrane proteins.
在过去的 20 年中，人们已经明显认识到真核细胞利用传统和非传统途径将蛋白质输送到其靶位。大多数带有信号肽和/或跨膜结构域的蛋白质通过内质网常规运输到高尔基体，然后再运输到质膜。然而，越来越多的可溶性货物（I 型、II 型和 III 型）和整合膜蛋白（IV 型）已被发现通过非常规蛋白质分泌 (UPS) 途径到达质膜，这些途径在某些条件下绕过高尔基体，例如细胞应激或发育。经历 IV 型 UPS 途径的跨膜蛋白的著名例子是位置特异性抗原亚单位 alpha 1 整合素、囊性纤维化跨膜电导调节剂、骨髓增生性白血病病毒癌基因和 pendrin。尽管我们统称所有绕过高尔基体的途径为 UPS，但与传统途径相比，个体运输途径是多样化的，UPS 途径的分子机制尚未完全确定。这篇综述总结了 UPS 货物蛋白，特别是具有跨膜结构域的 UPS 货物蛋白的细胞内运输途径，并讨论了跨膜蛋白 UPS 涉及的分子机制。
