Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii
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Uboldi, Alessandro D; Wilde, Mary-Louise; McRae, Emi A; Stewart, Rebecca J; Dagley, Laura F; Yang, Luning; Katris, Nicholas J; Hapuarachchi, Sanduni; Coffey, Michael J; Lehane, Adele; Botte, Cyrille Y; Waller, Ross F
Description
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...[Show more]
dc.contributor.author | Uboldi, Alessandro D | |
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dc.contributor.author | Wilde, Mary-Louise | |
dc.contributor.author | McRae, Emi A | |
dc.contributor.author | Stewart, Rebecca J | |
dc.contributor.author | Dagley, Laura F | |
dc.contributor.author | Yang, Luning | |
dc.contributor.author | Katris, Nicholas J | |
dc.contributor.author | Hapuarachchi, Sanduni | |
dc.contributor.author | Coffey, Michael J | |
dc.contributor.author | Lehane, Adele | |
dc.contributor.author | Botte, Cyrille Y | |
dc.contributor.author | Waller, Ross F | |
dc.date.accessioned | 2019-07-26T00:09:54Z | |
dc.date.available | 2019-07-26T00:09:54Z | |
dc.identifier.issn | 1544-9173 | |
dc.identifier.uri | http://hdl.handle.net/1885/164725 | |
dc.description.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 genetic depletion of PKAc1 we show that newly invaded parasites exit host cells shortly thereafter, in a perforin-like protein 1 (PLP-1)-dependent fashion. Furthermore, we demonstrate that loss of PKAc1 prevents rapid down-regulation of cytosolic [Ca2+] levels shortly after invasion. We also provide evidence that loss of PKAc1 sensitises parasites to cyclic GMP (cGMP)-induced Ca2+ signalling, thus demonstrating a functional link between cAMP and these other signalling modalities. Together, this work provides a new paradigm in understanding how Toxoplasma and related apicomplexan parasites regulate infectivity. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | Public Library of Science | |
dc.rights | © 2018 Uboldi et al. | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PLoS Biology | |
dc.title | Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 16 | |
dc.date.issued | 2018 | |
local.identifier.absfor | 060111 - Signal Transduction | |
local.identifier.ariespublication | u4485658xPUB1344 | |
local.publisher.url | https://www.plos.org/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Uboldi, Alessandro D, Walter and Eliza Hall Institute of Medical Research | |
local.contributor.affiliation | Wilde, Mary-Louise, University of Melbourne | |
local.contributor.affiliation | McRae, Emi A, University of Melbourne | |
local.contributor.affiliation | Stewart, Rebecca J, Walter and Eliza Hall Institute of Medical Research | |
local.contributor.affiliation | Dagley, Laura F, The Walter and Eliza Hall Institute of Medical Research | |
local.contributor.affiliation | Yang, Luning, The Walter and Eliza Hall Institute of Medical Research | |
local.contributor.affiliation | Katris, Nicholas J, University of Cambridge | |
local.contributor.affiliation | Hapuarachchi, Sanduni, College of Science, ANU | |
local.contributor.affiliation | Coffey, Michael J, The Walter and Eliza Hall Institute of Medical Research | |
local.contributor.affiliation | Lehane, Adele, College of Science, ANU | |
local.contributor.affiliation | Botte, Cyrille Y, Universite Grenoble Alpes | |
local.contributor.affiliation | Waller, Ross F, University of Melbourne | |
local.bibliographicCitation.issue | 9 | |
local.bibliographicCitation.startpage | 1 | |
local.bibliographicCitation.lastpage | 32 | |
local.identifier.doi | 10.1371/journal.pbio.2005642 | |
local.identifier.absseo | 920109 - Infectious Diseases | |
dc.date.updated | 2019-03-31T07:22:16Z | |
local.identifier.scopusID | 2-s2.0-85054816101 | |
dcterms.accessRights | Open Access | |
dc.provenance | © 2018 Uboldi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.rights.license | Creative Commons Attribution License | |
Collections | ANU Research Publications |
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