Back from the dormant stage: second messenger cyclic ADP-ribose essential for Toxoplasma gondii pathogenicity.

Abstract

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.

• Authors: Andreas H Guse
• Journal: Science signaling (Sci Signal) Vol. 1 Issue 17 Pg. pe18 (Apr 29 2008) ISSN: 1937-9145 [Electronic] United States
• PMID: 18445834 (Publication Type: Journal Article, Review)

Chemical References

• Cyclic ADP-Ribose
• GTP-Binding Proteins
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Signaling
• Cyclic ADP-Ribose (metabolism, physiology)
• GTP-Binding Proteins (metabolism)
• Gene Expression Regulation
• Mice
• Models, Biological
• Phosphorylation
• Second Messenger Systems
• Signal Transduction
• Symbiosis
• Toxoplasma (metabolism, pathogenicity)