TY - JOUR T1 - Evidence for a role of calcium in STING signaling JF - bioRxiv DO - 10.1101/145854 SP - 145854 AU - Sujeong Kim AU - Peter Koch AU - Lingyin Li AU - Leonid Peshkin AU - Timothy J. Mitchison Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/04/145854.abstract N2 - STING, an ER resident cyclic dinucleotide (CDN) receptor, plays an important role in innate immune response signaling. Upon binding to CDNs, it activates the TBK1-IRF3 signaling axis, which stimulates gene expression including interferon beta. We hypothesized that the ER localization of STING reflects a role for calcium mobilization in its signaling. To test this hypothesis, we treated mouse cells with two STING agonists, the synthetic drug DMXAA and a natural ligand, cyclic GMP-AMP (cGAMP), and measured intracellular calcium. Both triggered a rapid rise in intracellular calcium that was partially inhibited by STING depletion. Intracellular calcium chelation blocked DMXAA induced signaling downstream of STING activation, but had no effect on cGAMP induced signaling. We propose that intracellular calcium plays an important role in the response of the STING pathway. In response to DMXAA, calcium is mobilized form the ER and required for signaling. In the case of cGAMP calcium is mobilized but not required. This difference could be explained by alternative modes of STING activation for the two ligands, or a combination of STING-dependent and -independent actions of extracellular cGAMP. ER -