Calcium signaling through a transient receptor channel is important for Toxoplasma gondii growth

• Published in: eLife Vol. 10
• Main Authors: Márquez-Nogueras, Karla Marie, Hortua Triana, Miryam Andrea, Chasen, Nathan M, Kuo, Ivana Y, Moreno, Silvia NJ
• Format: Journal Article
• Language: English
• Published: Cambridge eLife Science Publications, Ltd 09.06.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Amino acids; Analysis; Calcium (extracellular); Calcium (intracellular); Calcium channels; calcium entry; Calcium influx; Calcium ions; calcium signaling; Calcium signalling; Cellular signal transduction; Endoplasmic reticulum; ER calcium; Genes; Genomes; Intracellular; Kidney diseases; Localization; Mass spectrometry; Microbiology and Infectious Disease; Nuclear membranes; Parasites; Patching; Physiological aspects; Properties; Proteins; Scientific imaging; Toxoplasma; Toxoplasma gondii; Toxoplasmosis; transient receptor channel; Transient receptor potential proteins; United States
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.63417

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.