Toxoplasma FER1 is a versatile and dynamic mediator of differential microneme trafficking and microneme exocytosis.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Exocytosis* ; Toxoplasma*/metabolism ; Protozoan Proteins*/metabolism ; Protein Transport*; Organelles/metabolism ; Humans ; Cell Membrane/metabolism

Toxoplasma gondii is a polarized cell concentrating several secretory organelles at the apical pole. The secretory micronemes come in two sub-populations differentiated by dependence on Rab5A/C in their biogenesis. Calcium-dependent exocytosis of micronemes occurs at the very apical tip and is critical for parasite egress from its host cell, adhesion and invasion of the next cell. Ferlins represent a protein family with roles in exocytosis containing multiple Ca ²⁺ -sensing C2 domains. We determined that T. gondii's ferlin 1 (FER1) localized dynamically to the parasite's secretory pathway. FER1 function was dissected by dominant negative overexpression strategies. We demonstrated that FER1 traffics microneme organelles along the following trajectories: (1) Along the cortex to the apical end; (2) To the apical tip for fusion with the plasma membrane; (3) Differential microneme sub-population traffic, and that FER1 could putatively be responsible for microneme protein trafficking. (4) From the trans-Golgi-endosomal network to the subpellicular cortex; (5) Retrograde transport allowing microneme recycling from mother to daughter. Finally, FER1 overexpression triggers a microneme exocytosis burst, supporting the notion that the radially organized micronemes at the apical tip comprise a readily-releasable microneme pool. In summary, FER1 is pivotal for dynamic microneme trafficking, acts differently on the two microneme subpopulations, and acts on the plasma membrane fusion step during microneme exocytosis.
(© 2024. The Author(s).)

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R03 AI122042 United States AI NIAID NIH HHS; AI108251 United States NH NIH HHS; AI122042 United States NH NIH HHS; RSG-12-175-01-MPC American Cancer Society; 1626072 National Science Foundation; AI060767 United States NH NIH HHS; RRP 12-175 United States HX HSRD VA

Keywords: Toxoplasma; Exocytosis; Ferlin; Microneme; Trafficking

0 (Protozoan Proteins)

Date Created: 20240918 Date Completed: 20240918 Latest Revision: 20240922

20250114

PMC11410953

10.1038/s41598-024-72628-0

39294204