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Updated: Oct 25, 2026

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Sensing a problem here: nucleotide signaling in immunity
Jocelyn Leon Padilla1, Eirene Marie Q Ednacot2, Benjamin R Morehouse3
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Abstract:
Cyclic nucleotides are shared messengers of antiviral immunity across bacteria and animals, yet the same chemical signal can produce strikingly different cellular outcomes. Recent studies show that bacteria generate the mammalian cGAS (cyclic GMP-AMP synthase product), 2'-5',3'-5'-cyclic GMP-AMP, during phage infection and use it to activate membrane-disrupting SAVED (SMODS-associated and fused to various effector domains)-family effectors. Structural work further reveals how ligand binding drives receptor oligomerization, filament formation, and vertical membrane shearing. In parallel, viral proteins that degrade or sequester cyclic nucleotides have exposed new evolutionary pressures on these pathways. We discuss how receptor architecture, supramolecular assembly, and antagonism determine signal meaning and how newly defined defense systems invert conventional signaling logic by sensing the loss rather than the production of an immune nucleotide.
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