title: A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP.
abstract: Second messengers are key components of many signal transduction pathways. In addition to cyclic AMP, ppGpp and cyclic di-GMP, many bacteria use also cyclic di-AMP as a second messenger. This molecule is synthesized by distinct classes of diadenylate cyclases and degraded by phosphodiesterases. The control of the intracellular c-di-AMP pool is very important since both a lack of this molecule and its accumulation can inhibit growth of the bacteria. In many firmicutes, c-di-AMP is essential, making it the only known essential second messenger. Cyclic di-AMP is implicated in a variety of functions in the cell, including cell wall metabolism, potassium homeostasis, DNA repair and the control of gene expression. To understand the molecular mechanisms behind these functions, targets of c-di-AMP have been identified and characterized. Interestingly, c-di-AMP can bind both proteins and RNA molecules. Several proteins that interact with c-di-AMP are required to control the intracellular potassium concentration. In Bacillus subtilis, c-di-AMP also binds a riboswitch that controls the expression of a potassium transporter. Thus, c-di-AMP is the only known second messenger that controls a biological process by interacting with both a protein and the riboswitch that regulates its expression. Moreover, in Listeria monocytogenes c-di-AMP controls the activity of pyruvate carboxylase, an enzyme that is required to replenish the citric acid cycle. Here, we review the components of the c-di-AMP signaling system.
authors: Department of General Microbiology, Georg-August-University Göttingen, Grisebachstr. 8, D-37077, Göttingen, Germany.
authors: Fabian M
authors: FM
authors: Commichau
authors: Department of Molecular Structural Biology, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, D-37077, Göttingen, Germany.
authors: Achim
authors: A
authors: Dickmanns
authors: Department of General Microbiology, Georg-August-University Göttingen, Grisebachstr. 8, D-37077, Göttingen, Germany.
authors: Jan
authors: J
authors: Gundlach
authors: Department of Molecular Structural Biology, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, D-37077, Göttingen, Germany.
authors: Ralf
authors: R
authors: Ficner
authors: Department of General Microbiology, Georg-August-University Göttingen, Grisebachstr. 8, D-37077, Göttingen, Germany.
authors: Jörg
authors: J
authors: Stülke
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism; D058928:Riboswitch; D015290:Second Messenger Systems
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D058928:Riboswitch; C528998:cyclic diadenosine phosphate; D010727:Phosphoric Diester Hydrolases; D011766:Pyruvate Carboxylase