Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth
Karla M. Márquez‐Nogueras, Miryam Andrea Hortua Triana, Nathan Michael Chasen, Ivana Y. Kuo, Silvia N.J. Moreno
Abstract
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.