Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth

Transient receptor potential (TRP) channels participate in calcium ion (Ca(2+)) influx and intracellular Ca(2+) release. TRP channels have not been studied in Toxoplasma gondii or any other apicomplexan parasite. In this work, we characterize TgGT1_310560, a protein predicted to possess a TRP domain (TgTRPPL-2), and determined its role in Ca(2+) signaling in T. gondii, the causative agent of toxoplasmosis. TgTRPPL-2 localizes to the plasma membrane and the endoplasmic reticulum (ER) of T. gondii. The ΔTgTRPPL-2 mutant was defective in growth and cytosolic Ca(2+) influx from both extracellular and intracellular sources. Heterologous expression of TgTRPPL-2 in HEK-3KO cells allowed its functional characterization. Patching of ER-nuclear membranes demonstrates that TgTRPPL-2 is a non-selective cation channel that conducts Ca(2+). Pharmacological blockers of TgTRPPL-2 inhibit Ca(2+) influx and parasite growth. This is the first report of an apicomplexan ion channel that conducts Ca(2+) and may initiate a Ca(2+) signaling cascade that leads to the stimulation of motility, invasion, and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.