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

  1. Karla Marie Marquez-Nogueras
  2. Myriam Andrea Hortua Triana
  3. Nathan M Chasen
  4. Ivana Y Kuo
  5. Silvia NJ Moreno  Is a corresponding author
  1. University of Georgia, United States
  2. Stritch School of Medicine, Loyola University, United States

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

  1. Karla Marie Marquez-Nogueras

    Microbiology, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
    ORCID icon "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.

Reviewing Editor

  1. Malcolm J McConville, The University of Melbourne, Australia

Version history

  1. Received: September 24, 2020
  2. Accepted: June 8, 2021
  3. Accepted Manuscript published: June 9, 2021 (version 1)
  4. Version of Record published: June 21, 2021 (version 2)

Copyright

© 2021, Marquez-Nogueras et al.

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.

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  1. Karla Marie Marquez-Nogueras
  2. Myriam Andrea Hortua Triana
  3. Nathan M Chasen
  4. Ivana Y Kuo
  5. Silvia NJ Moreno
(2021)
Calcium signaling through a Transient Receptor Channel is important for Toxoplasma gondii growth
eLife 10:e63417.
https://doi.org/10.7554/eLife.63417

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https://doi.org/10.7554/eLife.63417

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