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 Citations (Scopus)

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

Fingerprint

Cyclic ADP-Ribose
Toxoplasma
Ryanodine Receptor Calcium Release Channel
Calcium
ADP-ribosyl Cyclase
Microsomes
Parasites
Second Messenger Systems
Calcium Channels
Molecular Motor Proteins
Dantrolene
Ruthenium Red
Ryanodine
Exocytosis
Caffeine
Hydrolases
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii. / Chini, Eduardo N.; Nagamune, Kisaburo; Wetzel, Dawn M.; Sibley, L. David.

In: Biochemical Journal, Vol. 389, No. 2, 15.07.2005, p. 269-277.

Research output: Contribution to journalArticle

Chini, Eduardo N. ; Nagamune, Kisaburo ; Wetzel, Dawn M. ; Sibley, L. David. / Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii. In: Biochemical Journal. 2005 ; Vol. 389, No. 2. pp. 269-277.
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