Research Publications


An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca(2+) signalling and motility in Toxoplasma gondii

Yang, L; Uboldi, AD; Seizova, S; Wilde, ML; Coffey, MJ; Katris, NJ; Yamaryo-Botte, Y; Kocan, M; Bathgate, RAD; Stewart, RJ; McConville, MJ; Thompson, PE; Botte, CY; Tonkin, CJ
Journal of Biological Chemistry
Journal Article
Protozoan parasites of the phylum Apicomplexa actively move through tissue in order to initiate and perpetuate infection. The regulation of parasite motility relies on cyclic nucleotide-dependent kinases, but how these kinases are activated remains unknown. Here, using an array of biochemical and cell biology approaches, we show that the apicomplexan parasite Toxoplasma gondii expresses a large guanylate cyclase protein (TgGC), which contains several upstream ATPase transporter-like domains. We show that TgGC has a dynamic localization, being concentrated at the apical tip in extracellular parasites, which relocates to a more cytosolic distribution during intracellular replication. Conditional TgGC knockdown revealed that this protein is essential for acute-stage tachyzoite growth, as TgGC-deficient parasites were defective in motility, host cell attachment, invasion, and subsequent host cell egress. We show that TgGC is critical for a rapid rise in cytosolic [Ca(2+)] and for secretion of microneme organelles upon stimulation with a cGMP agonist, but these deficiencies can be bypassed by direct activation of signaling by a Ca(2+) ionophore. Further, we found that TgGC is required for transducing changes in extracellular pH and [K(+)] to activate cytosolic [Ca(2+)] flux. Together, the results of our work implicate TgGC as a putative signal transducer that activates Ca(2+) signaling and motility in Toxoplasma.
Infectious Diseases and Immune Defence
Refer to copyright notice on published article.

Creation Date 2019-04-26 10:14:46 Last Modified 2020-05-18 03:07:51