The fatal ADORAtion of adenosine based cyclic dinucleotides

What is it about?

By investigating the bioactivity of cyclic dinucleotides, a new class of microbial messengers and intracellular alarmins in mammalian cells, we described their unattended proapoptotic activity for human monocytes. They recognize selectively the adenosine-based cyclic dinucleotides by their cell surface adenosine receptor A2a, a Gas-coupled GPCR which signalling is turned off by the interaction. This signalling arrest induces formation of the mitochondrial permeability transition pore which inhibits mitochondrial respiration and causes apoptosis. Besides demonstrating the tonic signalling from A2a, this study constitutes the first report of a control of mitochondrial-induced cell death by GPCR in mammalian cells.

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Why is it important?

-GPCR signalling control cell death -GPCR are dependence receptors -Extracellular c-di-AMP and cGAMP induce apoptosis of human monocytes -c-di-AMP and cGAMP are antagonist ligands of the adenosine receptor A2a