The protozoan parasite Toxoplasma gondii relies on calcium-mediated exocytosis to secrete adhesins on to its surface where they can engage host cell receptors. Increases in intracellular calcium occur in response to Ins(1,4,5)P3 and caffeine, an agonist of ryanodine-responsive calcium-release channels. We examined lysates and microsomes of T. gondii and detected evidence of cADPR (cyclic ADP ribose) cyclase and hydrolase activities, the two enzymes that control the second messenger cADPR, which causes calcium release from RyR (ryanodine receptor). We also detected endogenous levels of cADPR in extracts of T. gondii. Furthermore, T. gondii microsomes that were loaded with 45Ca2+ released calcium when treated with cADPR, and the RyR antagonists 8-bromo-cADPR and Ruthenium Red blocked this response. Although T. gondii microsomes also responded to Ins(1,4,5)P3, the inhibition profiles of these calcium-release channels were mutually exclusive. The RyR antagonists 8-bromo-cADPR and dantrolene inhibited protein secretion and motility in live parasites. These results indicate that RyR calcium-release channels that respond to the second-messenger cADPR play an important role in regulating intracellular Ca2+, and hence host cell invasion, in protozoan parasites.
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Research Article|
July 05 2005
Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii
Eduardo N. Chini;
Eduardo N. Chini
*Department of Anesthesiology, Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN 55905, U.S.A.
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Kisaburo Nagamune;
Kisaburo Nagamune
†Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
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Dawn M. Wetzel;
Dawn M. Wetzel
†Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
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L. David Sibley
L. David Sibley
1
†Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
1To whom correspondence should be addressed (email sibley@borcim.wustl.edu).
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Publisher: Portland Press Ltd
Received:
November 29 2004
Revision Received:
February 14 2005
Accepted:
March 18 2005
Accepted Manuscript online:
March 18 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (2): 269–277.
Article history
Received:
November 29 2004
Revision Received:
February 14 2005
Accepted:
March 18 2005
Accepted Manuscript online:
March 18 2005
Citation
Eduardo N. Chini, Kisaburo Nagamune, Dawn M. Wetzel, L. David Sibley; Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii. Biochem J 15 July 2005; 389 (2): 269–277. doi: https://doi.org/10.1042/BJ20041971
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