Calcium signaling through a Transient Receptor Channel is important forToxoplasma gondiigrowth

Transient Receptor Potential (TRP) channels participate in ion calcium (Ca2+) influx and intracellular Ca2+release. TRP channels have not been studied inToxoplasma gondiior any other Apicomplexan parasite. We characterized a protein predicted to possess a TRP domain (TgTRPPL-2) and determined its role in Ca2+signaling inT. gondii, the causative agent of toxoplasmosis. TgTRPPL-2 localized to the plasma membrane and the endoplasmic reticulum ofT. gondii. TheΔTgTRPPL-2mutant was defective in growth and Ca2+influx. Heterologous expression of TgTRPPL-2 in HEK-3KO cells allowed its functional characterization. Patching of ER-nuclear membranes demonstrated that TgTRPPL-2 is a non-selective cation channel that conducts Ca2+. Pharmacological blockers of TgTRPPL-2 inhibited Ca2+influx and parasite growth. This is the first report of an Apicomplexan channel that conducts Ca2+and initiates the Ca2+signaling cascade that culminates in the stimulation of motility, invasion and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.