Transient Receptor Potential (TRP) channels participate in calcium ion (Ca2+) influx and intracellular Ca2+ 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 Ca2+ 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 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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Silvia NJ Moreno
- Silvia NJ Moreno
- Karla Marie Marquez-Nogueras
- Ivana Y Kuo
The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.
- Malcolm J McConville, The University of Melbourne, Australia
- Received: September 24, 2020
- Accepted: June 8, 2021
- Accepted Manuscript published: June 9, 2021 (version 1)
© 2021, Marquez-Nogueras et al.
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