Calcium-binding protein TgpCaBP regulates calcium storage of the zoonotic parasite Toxoplasma gondii

Abstract

ABSTRACT Toxoplasma gondii , the causative parasite of toxoplasmosis, is an apicomplexan parasite that infects warm-blooded mammals. The ability of the calcium-binding proteins (CBPs) to transport large amounts of Ca 2+ appears to be critical for the biological activity of T. gondii . However, the functions of some members of the CBP family have not yet been deciphered. Here, we characterized a putative CBP of T. gondii , TgpCaBP (TGME49_229480), which is composed of four EF-hand motifs with Ca 2+ -binding capability. TgpCaBP was localized in the cytosol and ER of T. gondii , and parasites lacking the TgpCaBP gene exhibited diminished abilities in cell invasion, intracellular growth, egress, and motility. These phenomena were due to the abnormalities in intracellular Ca 2+ efflux and ER Ca 2+ storage, and the reduction in motility was associated with a decrease in the discharge of secretory proteins. Therefore, we propose that TgpCaBP is a Ca 2+ transporter and signaling molecule involved in Ca 2+ regulation and parasitization in the hosts. IMPORTANCE Ca 2+ signaling is essential in the development of T. gondii . In this study, we identified a calcium-binding protein in T. gondii , named TgpCaBP, which actively regulates intracellular Ca 2+ levels in the parasite. Deletion of the gene coding for TgpCaBP caused serious deficits in the parasite’s ability to maintain a stable intracellular calcium environment, which also impaired the secretory protein discharged from the parasite, and its capacity of gliding motility, cell invasion, intracellular growth, and egress from host cells. In summary, we have identified a novel calcium-binding protein, TgpCaBP, in the zoonotic parasite T. gondii , which is a potential therapeutic target for toxoplasmosis.