How a key immune protein is regulated in the cell

The structure of AP-1 complexing with the STING cytosolic tail, which the researchers resolved at the Dubochet Center for Imaging (EPFL/UNIL/UNIGE) - Scientists at EPFL have determined how a protein that is critical in our first line of immune defense is regulated in the cell to prevent autoinflammatory diseases. How does a cell "know" that it's infected? This is a key question for innate immunity, our first line of defense to any infection or injury, made up of cells that quickly identify pathogens, like viral DNA. To do this, the cells use receptors that can identify nucleic acids - the building blocks of DNA - that in turn activate a signaling molecule called STING (for Stimulator of interferon genes). In a cascade of molecular "domino" - what scientists call a "signaling pathway" - STING begins to work after the enzyme cyclic GMP-AMP synthase, or cGAS, so the complete signaling pathway is known as cGAS-STING. Its role is to detect foreign DNA, e.g. from bacteria or viruses, that has invaded the cell. When foreign DNA invades the cell, the cGAS-STING signaling pathway turns on. STING exits the cell's endoplasmic reticulum where proteins are synthesized, and moves to the Golgi apparatus, where proteins undergo modifications and "final touches" before being packaged and sent to their target destination.