Calcium signaling through a Transient Receptor Channel is important forToxoplasma gondiigrowth

ABSTRACT Transient Receptor Potential (TRP) channels participate in ion calcium (Ca 2+ ) influx and intracellular Ca 2+ release. TRP channels have not been studied in Toxoplasma gondii or any other Apicomplexan parasite. We characterized 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 localized to the plasma membrane and the endoplasmic reticulum of T. gondii . The ΔTgTRPPL-2 mutant was defective in growth and Ca 2+ 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 Ca 2+ . Pharmacological blockers of TgTRPPL-2 inhibited Ca 2+ influx and parasite growth. This is the first report of an Apicomplexan channel that conducts Ca 2+ and initiates the Ca 2+ signaling cascade that culminates in the stimulation of motility, invasion and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.