Back from the dormant stage: second messenger cyclic ADP-ribose essential for Toxoplasma gondii pathogenicity.
Cyclic adenosine diphosphoribose (cADPR) is an endogenous Ca2+-mobilizing second messenger found in cells of animals, plants, and protozoans. It is formed by a specific class of enzymes, the ADP-ribosyl cyclases. cADPR stimulates Ca2+ release by means of ryanodine receptors located in the sarcoplasmic and endoplasmic reticulum. Recently, a role for cADPR has been demonstrated in the obligate intracellular protozoan pathogen Toxoplasma gondii. In T. gondii, stress conditions evoked synthesis of the plant hormone abscisic acid by the apicoplast, a remnant organelle of an algal endosymbiont of T. gondii. Abscisic acid in turn activated formation of cADPR within T. gondii, resulting in Ca2+ release and secretion of proteins involved in egress of T. gondii from its host cell. Evidence for a synthetic pathway of plant origin was obtained with the ABA synthesis inhibitor fluridone, which antagonized cellular egress and induced differentiation of long-lived semidormant cystic forms of T. gondii. Moreover, fluridone protected mice from toxoplasmosis.
Guse
Andreas H
AH
The Calcium Signalling Group, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, Centre of Experimental Medicine, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. guse@uke.uni-hamburg.de
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D036563:Cyclic ADP-Ribose / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D015290:Second Messenger Systems; D015398:Signal Transduction; D013559:Symbiosis; D014122:Toxoplasma / Q000378:metabolism* / Q000472:pathogenicity
D036563:Cyclic ADP-Ribose; D019204:GTP-Binding Proteins; D002118:Calcium