Cyclic di-AMP: another second messenger enters the fray

Cyclic di-AMP is one of the latest cyclic nucleotide second messengers to be discovered in bacteria. Here, Corrigan and Gründling provide an overview of the enzymes involved in its synthesis and degradation, the currently known receptor proteins and the cellular pathways that are known to be directly or indirectly controlled by this newly identified second messenger. Nucleotide signalling molecules contribute to the regulation of cellular pathways in all forms of life. In recent years, the discovery of new signalling molecules in bacteria and archaea, as well as the elucidation of the pathways they regulate, has brought insights into signalling mechanisms not only in bacterial and archaeal cells but also in eukaryotic host cells. Here, we provide an overview of the synthesis and regulation of cyclic di-AMP (c-di-AMP), one of the latest cyclic nucleotide second messengers to be discovered in bacteria. We also discuss the currently known receptor proteins and pathways that are directly or indirectly controlled by c-di-AMP, the domain structure of the enzymes involved in its production and degradation, and the recognition of c-di-AMP by the eukaryotic host.