Identification of extracellular membrane protein ENPP3 as a major cGAMP hydrolase, cementing cGAMP’s role as an immunotransmitter
Rachel Mardjuki,
Songnan Wang,
Jacqueline A. Carozza
et al.
Abstract:cGAMP is a second messenger that is synthesized in the cytosol upon detection of cytosolic dsDNA and passed between cells to facilitate downstream immune signaling. ENPP1, an extracellular enzyme, was the only metazoan cGAMP hydrolase known to regulate cGAMP levels to dampen anti-cancer immunity. Here, we uncover ENPP3 as the second and only other metazoan cGAMP hydrolase under homeostatic conditions. ENPP3 has a tissue expression pattern distinct from that of ENPP1 and accounts for all remaining cGAMP hydroly… Show more
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