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Toxoplasma gondii microneme secretion involves intracellular Ca(2+) release from inositol 1,4,5-triphosphate
Jennie L Lovett1, Norma Marchesini, Silvia N J Moreno
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract:
Calcium-mediated microneme secretion in Toxoplasma gondii is stimulated by contact with host cells, resulting in the discharge of adhesins that mediate attachment. The intracellular source of calcium and the signaling pathway(s) triggering release have not been characterized, prompting our search for mediators of calcium signaling and microneme secretion in T. gondii. We identified two stimuli of microneme secretion, ryanodine and caffeine, which enhanced release of calcium from parasite intracellular stores. Ethanol, a previously characterized trigger of microneme secretion, stimulated an increase in parasite inositol 1,4,5-triphosphate, implying that this second messenger may mediate intracellular calcium release. Consistent with this observation, xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, inhibited microneme secretion and blocked parasite attachment and invasion of host cells. Collectively, these results suggest that T. gondii possess an intracellular calcium release channel with properties of the inositol 1,4,5-triphosphate/ryanodine receptor superfamily. Intracellular calcium channels, previously studied almost exclusively in multicellular animals, appear to also be critical to the control of parasite calcium during the initial steps of host cell entry.
Insights
Toxoplasma gondii uses intracellular calcium stores to release microneme adhesins for host cell invasion. Ryanodine, caffeine, and inositol 1,4,5-triphosphate signaling mediate this critical calcium release process.
Area of Science:
- Parasitology
- Cell Biology
- Molecular Biology
Background:
- Microneme secretion in *Toxoplasma gondii* is crucial for host cell attachment and invasion.
- The intracellular calcium sources and signaling pathways regulating microneme secretion remain largely uncharacterized.
Purpose of the Study:
- To identify mediators of calcium signaling and microneme secretion in *Toxoplasma gondii*.
- To elucidate the role of intracellular calcium release in parasite invasion.
Main Methods:
- Stimulation of *T. gondii* with ryanodine, caffeine, and ethanol.
- Measurement of intracellular calcium release and inositol 1,4,5-triphosphate levels.
- Assessment of microneme secretion, attachment, and invasion using xestospongin C.
Main Results:
- Ryanodine and caffeine stimulated calcium release from intracellular stores.
- Ethanol increased inositol 1,4,5-triphosphate, suggesting its role in calcium release.
- Xestospongin C inhibited microneme secretion, attachment, and invasion, indicating involvement of inositol 1,4,5-triphosphate receptors.
Conclusions:
- *T. gondii* possesses intracellular calcium release channels similar to inositol 1,4,5-triphosphate/ryanodine receptors.
- These channels are critical for regulating parasite calcium during host cell entry.
- Intracellular calcium signaling is essential for the initial steps of *Toxoplasma* infection.