The journey of STING: Guiding immune signaling through membrane trafficking

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.