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Biology subjects

Vella, S. A.

Publications and source records attributed to Vella, S. A..

2 recordsLinked to original sources

The Role of Host Calcium Signaling in Toxoplasma gondii egress

Toxoplasma gondii, an obligate intracellular parasite, is capable of invading virtually any nucleated cell. Ca2+ signaling is universal and both T. gondii and its mammalian host cell will utilize Ca2+ signaling to stimulate diverse cellular functions. Egress of T. gondii from the host cell is an essential step for the infection cycle of T. gondii and a cytosolic Ca2+ increase initiates the Ca2+ signaling cascade that culminates in stimulation of motility and egress. In this work we demonstrate that intracellular T. gondii is capable of taking up Ca2+ from the host cytoplasm when this concentration is increased during host signaling events. Both intracellular and extracellular Ca2+ sources are important to reach a threshold of cytosolic Ca2+ needed for a successful egress. Two peaks of Ca2+ were observed in single parasites that egressed with the second peak resulting from Ca2+ influx. We patched infected host cells to allow a precise delivery of exact concentrations of Ca2+ for stimulating motility and egress. Using this approach, we found that low potassium concentration modulates but do not trigger host cell egress. This is the first study using whole-cell patches to study the role of ions such as K+ and Ca2+ in T. gondii egress.

microbiology↗

The Toxoplasma Vacuolar H+-ATPase regulates intracellular pH, and impacts the maturation of essential secretory proteins

Vacuolar-proton ATPases (V-H+-ATPases) are conserved complexes that couple the hydrolysis of ATP to the pumping of protons across membranes. V-H+-ATPases are known to play diverse roles in cellular physiology. We studied the Toxoplasma gondii V-H+-ATPase complex and discovered a novel dual role of the pump in protecting parasites against ionic stress and in the maturation of secretory proteins in endosomal-like compartments. Toxoplasma V-H+-ATPase subunits localize to the plasma membrane and to acidic vesicles and characterization of conditional mutants of the a1 subunit highlighted the functionality of the complex at both locations. Microneme and rhoptry proteins are required for invasion and modulation of host cells and they traffic via endosome-like compartments in which proteolytic maturation occurs. We show that the V-H+-ATPase supports the maturation of rhoptry and microneme proteins, and their maturases, during their traffic to their corresponding organelles. This work underscores a novel role for V-H+-ATPases in regulating virulence pathways.

microbiology↗