Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
Cytokine Growth Factor Rev. 2024 Aug;78:25-36. doi: 10.1016/j.cytogfr.2024.07.003. Epub 2024 Jul 6.
Stimulator of Interferon Genes (STING) serves as a pivotal mediator in the innate immune signaling pathway, transducing signals from various DNA receptors and playing a crucial role in natural immune processes. During cellular quiescence, STING protein resides in the endoplasmic reticulum (ER), and its activation typically occurs through the cGAS-STING signaling pathway. Upon activation, STING protein is transported to the Golgi apparatus, thereby initiating downstream signaling cascades. Vesicular transport serves as the primary mechanism for STING protein trafficking between the ER and Golgi apparatus, with COPII mediating anterograde transport from the ER to Golgi apparatus, while COPI is responsible for retrograde transport. Numerous factors influence these transport processes, thereby exerting either promoting or inhibitory effects on STING protein expression. Upon reaching the Golgi apparatus, to prevent over-activation, STING protein is transported to post-Golgi compartments for degradation. In addition to the conventional lysosomal degradation pathway, ESCRT has also been identified as one of the degradation pathways for STING protein. This review summarizes the recent findings on the membrane trafficking pathways of STING, highlighting their contributions to the regulation of cytokine production, the activation of immune cells, and the coordination of immune signaling pathways.
干扰素基因刺激物 (STING) 作为先天免疫信号通路中的关键介质，可将来自各种 DNA 受体的信号转导，并在天然免疫过程中发挥关键作用。在细胞静止期，STING 蛋白位于内质网 (ER) 中，其激活通常通过 cGAS-STING 信号通路发生。激活后，STING 蛋白被运送到高尔基器，从而启动下游信号级联反应。囊泡运输是 ER 和高尔基器之间 STING 蛋白运输的主要机制，COPII 介导内质网到高尔基器的正向运输，而 COPI 负责逆行运输。许多因素影响这些运输过程，从而对 STING 蛋白表达产生促进或抑制作用。到达高尔基器后，为防止过度激活，STING 蛋白被运送到高尔基器后区进行降解。除了传统的溶酶体降解途径外，ESCRT 也被鉴定为 STING 蛋白的降解途径之一。本综述总结了 STING 膜运输途径的最新发现，强调了它们在细胞因子产生的调节、免疫细胞的激活以及免疫信号通路的协调中的作用。
