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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.

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Resource Type: Bibliography, Diagram, Illustration, Journal article/Issue, Review
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright

Authors and Editors: Andreas H. Guse of Institute of Biochemistry and Molecular Biology and Centre of Experimental Medicine, University Medical Centre Hamburg-Eppendorf
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes


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