STAM transports STING oligomers into extracellular vesicles, down-regulating the innate immune response

Stimulator of interferon genes (STING) mediates the innate immune response against damaged endogenous double-strand DNA and exogenous virus infection. The location of STING is critical to the accurate control of defence signalling pathways. Recently, the effects of extracellular vesicles (EVs) in the regulation of innate immune signalling have been reported. Nevertheless, the particular roles played by STING in EVs and the related mechanisms have remained largely unknown.

Researchers from Tsinghua University report that when STING was activated in cells, EVs derived from these cells carried STING oligomers. Signal transducing adapter molecule 1 (STAM) was found to be a STING transporter that directly interacted with STING and facilitated STING transport into EVs. Importantly, the translocation of STING into EVs was a mechanism by which STING was degraded, suppressing the innate immune response.

A mechanism model of STAM-mediated STING oligomer transportation
into extracellular vesicles

After STING signalling pathway is activated, STING is translocated from ER to the Golgi apparatus with the help of STEEP or other interacted proteins. STING is phosphorylated (p) and forms oligomers on the Golgi apparatus, and then triggers the downstream signalling. Meanwhile, STAM is induced, interacts with STING, and transports STING to the multivesicular bodies. Finally, STING is carried into EVs and released from the cell. This STING secretion pathway shows a novel way for removal, hence inactivation, of STING, thereby suppressing the innate immune response, which may prevent overactivation.