Ferlins and TgDOC2 in Toxoplasma Microneme, Rhoptry and Dense Granule Secretion

Area of Science:

• Parasitology
• Cell Biology
• Molecular Biology

Background:

• Apicomplexan parasites like *Toxoplasma gondii* invade host cells via sequential exocytosis of specialized organelles.
• This process relies on proteins with C2 domains, including ferlins and double C2 domain (DOC2) proteins.
• Calcium ions (Ca²⁺) play a critical role in regulating these exocytosis events.

Purpose of the Study:

• To investigate the roles of ferlins and TgDOC2 in apicomplexan organelle exocytosis.
• To explore the mechanisms by which Ca²⁺, lipids, and post-translational modifications facilitate sequential exocytosis.
• To present new findings on the cross-talk between secretion events and identify a novel microneme protein, MIC21.

Main Methods:

• Analysis of conserved ferlin and DOC2 protein families in *Toxoplasma gondii*.
• Investigation of calcium-dependent protein-lipid and protein-protein interactions.
• Examination of the functional roles of FER1, FER2, and TgDOC2 in exocytosis pathways.
• Identification and characterization of new secretory pathway components.

Main Results:

• The *T. gondii* ferlins FER1 and FER2 are essential for microneme and rhoptry exocytosis, respectively.
• An unconventional TgDOC2 protein is critical for microneme exocytosis.
• Ferlins demonstrate the capacity to mediate membrane fusion independently of SNARE proteins.
• New data reveals cross-talk between different secretion events and identifies MIC21.

Conclusions:

• Ferlin and DOC2 proteins are key regulators of sequential exocytosis in apicomplexan parasites.
• Calcium signaling, membrane lipids, and post-translational modifications orchestrate these complex secretory events.
• Understanding these mechanisms provides insights into apicomplexan host cell invasion and potential therapeutic targets.