Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii

Eduardo N. Chini, Kisaburo Nagamune, Dawn M. Wetzel, L. David Sibley

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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)P 3, 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.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalBiochemical Journal
Volume389
Issue number2
DOIs
StatePublished - Jul 15 2005

Keywords

  • Calcium channel
  • Cyclic ADP ribose (cADPR)
  • Microneme secretion
  • Parasite
  • Signalling

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