Toxoplasma ferlin1 is a versatile and dynamic mediator of microneme trafficking and secretion
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 the 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 Ca2+-sensing C2 domains. We determined that T. gondiis ferlin 1 (FER1) localized dynamically to the parasites secretory pathway. FER1 function was dissected by dominant negative overexpression strategies. We demonstrated that FER1 traffics microneme organelles along the following trajectories:1. From the trans-Golgi-endosomes network to the subpellicular cortex; 2. Along the cortex to the apical end; 3. To the apical tip for fusion with the plasma membrane; 4. Retrograde transport allowing microneme recycling from mother to daughter; 5. Differential microneme sub-population traffic. 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.