title: Cyclic di-nucleotide signaling enters the eukaryote domain.
abstract: Cyclic (c-di-GMP) is the prevalent intracellular signaling intermediate in bacteria. It triggers a spectrum of responses that cause bacteria to shift from a swarming motile phase to sessile biofilm formation. However, additional functions for c-di-GMP and roles for related molecules, such as c-di-AMP and c-AMP-GMP continue to be uncovered. The first usage of cyclic-di-nucleotide (c-di-NMP) signaling in the eukaryote domain emerged only recently. In dictyostelid social amoebas, c-di-GMP is a secreted signal that induces motile amoebas to differentiate into sessile stalk cells. In humans, c-di-NMPs, which are either produced endogenously in response to foreign DNA or by invading bacterial pathogens, trigger the innate immune system by activating the expression of interferon genes. STING, the human c-di-NMP receptor, is conserved throughout metazoa and their closest unicellular relatives, suggesting protist origins for human c-di-NMP signaling. Compared to the limited number of conserved protein domains that detect the second messengers cAMP and cGMP, the domains that detect the c-di-NMPs are surprisingly varied.
authors.affiliation: College of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Pauline
authors.initials: P
authors.lastname: Schaap
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000502:physiology; D004023:Dictyostelium / Q000502:physiology; D015226:Dinucleoside Phosphates / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D009712:Nucleotides, Cyclic / Q000096:biosynthesis; D009713:Nucleotidyltransferases / Q000235:genetics; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology*; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D001426:Bacterial Proteins; D006152:Cyclic GMP; D015226:Dinucleoside Phosphates; D008565:Membrane Proteins; D009712:Nucleotides, Cyclic; D009713:Nucleotidyltransferases; C532857:STING1 protein, human; D000099197:STING Protein; C528998:cyclic diadenosine phosphate; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C062025:bis(3',5')-cyclic diguanylic acid; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: 2′3′-cGAMP; Dictyostelium; STING; biofilm; cGAS; cyclic di-AMP; cyclic di-GMP; diadenylate cyclase; diguanylate cyclase; stalk cell differentiation