Protein kinase A negatively regulates Ca2 signalling in Toxoplasma gondii

Alessandro D Uboldi; Mary-Louise Wilde; Emi A McRae; Rebecca J Stewart; Laura F Dagley; Luning Yang; Nicholas J Katris; Sanduni Hapuarachchi; Michael J Coffey; Adele M Lehane; Cyrille Y Botte; Ross F Waller; Andrew Webb; Malcolm J McConville; Christopher J Tonkin

Journal article

Protein kinase A negatively regulates Ca2 signalling in Toxoplasma gondii

Alessandro D Uboldi, Mary-Louise Wilde, Emi A McRae, Rebecca J Stewart, Laura F Dagley, Luning Yang, Nicholas J Katris, Sanduni Hapuarachchi, Michael J Coffey, Adele M Lehane, Cyrille Y Botte, Ross F Waller, Andrew Webb, Malcolm J McConville, Christopher J Tonkin

PLOS BIOLOGY | PUBLIC LIBRARY SCIENCE | Published : 2018

DOI: 10.1371/journal.pbio.2005642

Download PDF

Abstract

The phylum Apicomplexa comprises a group of obligate intracellular parasites that alternate between intracellular replicating stages and actively motile extracellular forms that move through tissue. Parasite cytosolic Ca2+ signalling activates motility, but how this is switched off after invasion is complete to allow for replication to begin is not understood. Here, we show that the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1 (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host cell invasion. We demonstrate that PKAc1 is sequestered to the parasite periphery by dual acylation of PKA regulatory subunit 1 (PKAr1). Upon genet..

View full abstract

University of Melbourne Researchers

Christopher Tonkin Author Medical Biology (W.E.H.I.)

Malcolm McConville Author Biochemistry and Pharmacology

Andrew Webb Author Medical Biology (W.E.H.I.)

Laura Dagley Author Medical Biology (W.E.H.I.)

Alessandro Uboldi Author Medical Biology (W.E.H.I.)

Related Projects (1)

TARGETING ACUTE AND CHRONIC TOXOPLASMOSIS

One third of the world's population is infected with the protozoan parasite, Toxoplasma gondii, which can cause life-threatening infections...

Grants

Awarded by National Health and Medical Research Council

Awarded by Australian Research Council

Awarded by Agence Nationale de la Recherche

Awarded by Medical Research Council (MRC) UK

Funding Acknowledgements

National Health and Medical Research Council (grant number APP1123218, APP1047806, APP1025598). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Australian Research Council (grant number FT120100164, DE160101035). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Agence Nationale de la Recherche (grant number LABEX PARAFRAP ANR-11-LABX-0024). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CNRS-INSERM-Fondation FINOVI. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Victorian State Government Operational Infrastructure Support and the Australian Government. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council (MRC) UK (grant number MR/M011690/1). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. China Council. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.