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

Area of Science:

• Molecular Parasitology
• Ion Channel Biology
• Calcium Signaling

Background:

• Transient receptor potential (TRP) channels regulate calcium ion (Ca²⁺) flux but remain uncharacterized in apicomplexan parasites like *Toxoplasma gondii*.
• *Toxoplasma gondii* is the causative agent of toxoplasmosis, a significant public health concern.

Purpose of the Study:

• To characterize the TgTRPPL-2 protein, a putative TRP channel in *T. gondii*.
• To determine the role of TgTRPPL-2 in calcium (Ca²⁺) signaling and parasite biology.

Main Methods:

• Localization studies of TgTRPPL-2 within *T. gondii* cells (plasma membrane and endoplasmic reticulum).
• Generation and analysis of a *ΔTgTRPPL-2* knockout mutant.
• Heterologous expression of TgTRPPL-2 in HEK-3KO cells for functional characterization using patch-clamp electrophysiology.
• Assessment of the effects of pharmacological blockers on Ca²⁺ influx and parasite growth.

Main Results:

• TgTRPPL-2 localizes to the plasma membrane and ER of *T. gondii*.
• The *ΔTgTRPPL-2* mutant exhibits defects in growth and cytosolic Ca²⁺ influx from both extracellular and intracellular stores.
• Functional characterization reveals TgTRPPL-2 as a non-selective cation channel conducting Ca²⁺ across ER-nuclear membranes.
• Pharmacological inhibition of TgTRPPL-2 significantly reduces Ca²⁺ influx and parasite growth.

Conclusions:

• TgTRPPL-2 is the first identified apicomplexan ion channel that conducts Ca²⁺.
• This channel likely initiates Ca²⁺ signaling cascades essential for parasite motility, invasion, and egress.
• TgTRPPL-2 represents a promising therapeutic target for combating toxoplasmosis.