Journal article

An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca2 signaling and motility in Toxoplasma gondii

Luning Yang, Alessandro D Uboldi, Simona Seizova, Mary-Louise Wilde, Michael J Coffey, Nicholas J Katris, Yoshiki Yamaryo-Botte, Martina Kocan, Ross AD Bathgate, Rebecca J Stewart, Malcolm J McConville, Philip E Thompson, Cyrille Y Botte, Christopher J Tonkin

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2019

Abstract

Protozoan parasites of the phylum Apicomplexa actively move through tissue 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 (TgGC) protein, 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 then relocates to a more cytosolic distribution during intracellular replication. Conditional T..

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Grants

Awarded by Australian Research Council (ARC) Future Fellowship


Awarded by Agence Nationale de la Recherche, France


Awarded by Laboratoire d' Excellence Parafrap, France


Funding Acknowledgements

This work was supported by Australian Research Council (ARC) Future Fellowship FT120100164 (to C.J.T.); a China Council scholarship (to L.Y.); Victorian State Government Operational Infrastructure Support and the Australian Government National Health and Medical Research Council (NHMRC) Independent Medical Research Institutes Infrastructure Support Scheme (IRIISS); Agence Nationale de la Recherche, France Grant ANR-12-PDOC-0028-Project Apicolipid, the Atip-Avenir and Finovi programs (CNRS-INSERM-FinoviAtip-Avenir Apicolipid projects), and Laboratoire d' Excellence Parafrap, France Grant ANR-11-LABX-0024 (to C.Y.B., Y.Y.-B., and N.J.K.); the Laboratoire International Associe (LIA) CNRS Program (Apicolipid project) (to C.Y.B. and C.J.T.); and an NHMR Cprinciple research fellowship (to M.J.M.).