Calcium signaling through a transient receptor channel is important for <i>Toxoplasma gondii</i> growth.

Abstract

Transient receptor potential (TRP) channels participate in calcium ion (Ca²⁺) influx and intracellular Ca²⁺ release. TRP channels have not been studied in <i>Toxoplasma gondii</i> 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 Ca²⁺ signaling in <i>T. gondii</i>, the causative agent of toxoplasmosis. TgTRPPL-2 localizes to the plasma membrane and the endoplasmic reticulum (ER) of <i>T. gondii</i>. The <i>ΔTgTRPPL-2</i> mutant was defective in growth and cytosolic Ca²⁺ 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 Ca²⁺. Pharmacological blockers of TgTRPPL-2 inhibit Ca²⁺ influx and parasite growth. This is the first report of an apicomplexan ion channel that conducts Ca²⁺ and may initiate a Ca²⁺ signaling cascade that leads to the stimulation of motility, invasion, and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.