The Toxoplasma Vacuolar H+-ATPase Regulates Intracellular pH and Impacts the Maturation of Essential Secretory Proteins

摘要

Vacuolar-proton ATPases (V-ATPases) are conservedcomplexes that couple the hydrolysis of ATP to thepumping of protons across membranes. V-ATPasesare known to play diverse roles in cellular physiology.We studied the Toxoplasma gondii V-ATPasecomplex and discovered a dual role of the pump inprotecting parasites against ionic stress and inthe maturation of secretory proteins in endosomallikecompartments. Toxoplasma V-ATPase subunitslocalize to the plasma membrane and to acidic vesicles,and characterization of conditional mutants ofthe a1 subunit highlighted the functionality of thecomplex at both locations. Microneme and rhoptryproteins are required for invasion and modulation ofhost cells, and they traffic via endosome-like compartmentsin which proteolytic maturation occurs.We show that the V-ATPase supports the maturationof rhoptry and microneme proteins, and their maturases,during their traffic to their corresponding organelles.This work underscores a role for V-ATPasesin regulating virulence pathways.