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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
2019-07
2019-04-16
Journal of Biological Chemistry
Journal Article
21
7
e13030
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.
ASBMB
Infectious Diseases and Immune Defence
10.1074/jbc.RA118.005491
30992368
Refer to copyright notice on published article.

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