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

eLife

Miryam Andrea Hortua Triana¹  Nathan M Chasen¹  Karla Marie Márquez-Nogueras²  Silvia NJ Moreno³  Ivana Y Kuo⁴ 

[1] Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States;Center 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 States;Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States;Department of Cellular Biology, University of Georgia, Athens, United States;Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, United States;

关键词: Toxoplasma gondii;    calcium signaling;    transient receptor channel;    calcium entry;    ER calcium;    Other;   

DOI  :  10.7554/eLife.63417

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY