Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth
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 (Tg...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63417 |
| _version_ | 1811180595241287680 |
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| author | Karla Marie Márquez-Nogueras Miryam Andrea Hortua Triana Nathan M Chasen Ivana Y Kuo Silvia NJ Moreno |
| author_facet | Karla Marie Márquez-Nogueras Miryam Andrea Hortua Triana Nathan M Chasen Ivana Y Kuo Silvia NJ Moreno |
| author_sort | Karla Marie Márquez-Nogueras |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:06:00Z |
| format | Article |
| id | doaj.art-447eb7e63c784937a8a63cc25a658255 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:00Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-447eb7e63c784937a8a63cc25a6582552022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.63417Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growthKarla Marie Márquez-Nogueras0https://orcid.org/0000-0002-9459-6882Miryam Andrea Hortua Triana1Nathan M Chasen2Ivana Y Kuo3https://orcid.org/0000-0002-9867-2408Silvia NJ Moreno4https://orcid.org/0000-0002-2041-6295Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States; Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, United StatesCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, United StatesCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, United StatesDepartment of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, United StatesCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States; Department of Cellular Biology, University of Georgia, Athens, United StatesTransient 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.https://elifesciences.org/articles/63417Toxoplasma gondiicalcium signalingtransient receptor channelcalcium entryER calcium |
| spellingShingle | Karla Marie Márquez-Nogueras Miryam Andrea Hortua Triana Nathan M Chasen Ivana Y Kuo Silvia NJ Moreno Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth eLife Toxoplasma gondii calcium signaling transient receptor channel calcium entry ER calcium |
| title | Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth |
| title_full | Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth |
| title_fullStr | Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth |
| title_full_unstemmed | Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth |
| title_short | Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth |
| title_sort | calcium signaling through a transient receptor channel is important for toxoplasma gondii growth |
| topic | Toxoplasma gondii calcium signaling transient receptor channel calcium entry ER calcium |
| url | https://elifesciences.org/articles/63417 |
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