School of Pharmacy, Queen's University Belfast, Belfast, UK.
Traffic. 2024 Feb;25(2):e12931. doi: 10.1111/tra.12931.
Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins that become mis-localised. However, aberrant RT can alter the correct location of key proteins, and thus inhibit or indeed change their canonical function, potentially causing disease. This review highlights the recent advances in the understanding of how upregulation, downregulation or hijacking of RT impacts the localisation of key proteins in cancer and disease to drive progression. Cargoes impacted by aberrant RT are varied amongst maladies including neurodegenerative diseases, autoimmune diseases, bacterial and viral infections (including SARS-CoV-2), and cancer. As we explore the intricacies of RT, it becomes increasingly apparent that it holds significant potential as a target for future therapies to offer more effective interventions in a wide range of pathological conditions.
逆行转运 (RT) 以向内/ER 定向的方式协调货物从质膜、内体、高尔基体或内质网-高尔基体中间池 (ERGIC) 向细胞内的运动。RT 与正向转运 (向外分泌) 相反，两者共同作用以维持细胞内稳态。这是通过维持细胞极性、回收负责正向转运的蛋白质和重定向定位错误的蛋白质来实现的。然而，异常的 RT 会改变关键蛋白的正确位置，从而抑制或改变其经典功能，从而导致疾病。本综述强调了近年来对 RT 的上调、下调或劫持如何影响癌症和疾病中关键蛋白定位以推动进展的理解的最新进展。受异常 RT 影响的货物在神经退行性疾病、自身免疫性疾病、细菌和病毒感染（包括 SARS-CoV-2）以及癌症等多种疾病中各不相同。随着我们探索 RT 的复杂性，越来越明显的是，它作为未来治疗靶点具有很大的潜力，可以在广泛的病理条件下提供更有效的干预措施。
