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

Author(s): 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;
Details: Publication Year 2019-07,Volume 21,Issue #7,Page e13030
Journal Title: Journal of Biological Chemistry
Publication Type: Journal Article
Abstract: 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.
Publisher: ASBMB
Research Division(s): Infectious Diseases And Immune Defence
PubMed ID: 30992368
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552420/
Publisher's Version: https://doi.org/10.1074/jbc.RA118.005491
ARC Grants: ARC/FT120100164,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-04-26 10:14:46

Last Modified: 2020-05-18 03:07:51