Calcium signaling through a Transient Receptor Channel is important for Toxoplasma gondii growth

Abstract
Data availability
Article and author information
Metrics

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

Karla Marie Marquez-Nogueras

Microbiology, University of Georgia, Athens, United States

Competing interests
The authors declare that no competing interests exist.
Myriam Andrea Hortua Triana

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States

Competing interests
The authors declare that no competing interests exist.
Nathan M Chasen

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States

Competing interests
The authors declare that no competing interests exist.
Ivana Y Kuo

Cell and Molecular Physiology, Stritch School of Medicine, Loyola University, Chicago, United States

Competing interests
The authors declare that no competing interests exist.
Silvia NJ Moreno

Cellular Biology, University of Georgia, Athens, United States

For correspondence
smoreno@uga.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2041-6295

Funding

National Institutes of Health (AI154931)

Silvia NJ Moreno

National Institutes of Health (AI128356)

Silvia NJ Moreno

National Institutes of Health (T32AI060546)

Karla Marie Marquez-Nogueras

National Institutes of Health (DK101585)

Ivana Y Kuo

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.