A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
24
08
2022
accepted:
29
09
2022
revised:
01
11
2022
pubmed:
21
10
2022
medline:
4
11
2022
entrez:
20
10
2022
Statut:
epublish
Résumé
Fundamental processes that govern the lytic cycle of the intracellular parasite Toxoplasma gondii are regulated by several signalling pathways. However, how these pathways are connected remains largely unknown. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels. We show that both egress inducers trigger indistinguishable signalling responses and provide evidence for a positive feedback loop linking calcium and cyclic nucleotide signalling. Using WT and conditional knockout parasites of the non-essential calcium-dependent protein kinase 3 (CDPK3), which display a delay in calcium inonophore-mediated egress, we explore changes in phosphorylation and lipid signalling in sub-minute timecourses after inducing Ca2+ release. These studies indicate that cAMP and lipid metabolism are central to the feedback loop, which is partly dependent on CDPK3 and allows the parasite to respond faster to inducers of egress. Biochemical analysis of 4 phosphodiesterases (PDEs) identified in our phosphoproteomes establishes PDE2 as a cAMP-specific PDE which regulates Ca2+ induced egress in a CDPK3-independent manner. The other PDEs display dual hydrolytic activity and play no role in Ca2+ induced egress. In summary, we uncover a positive feedback loop that enhances signalling during egress, thereby linking several signalling pathways.
Identifiants
pubmed: 36265000
doi: 10.1371/journal.ppat.1010901
pii: PPATHOGENS-D-22-01475
pmc: PMC9624417
doi:
Substances chimiques
Calcium
SY7Q814VUP
Nucleotides, Cyclic
0
diethylstilbestrol monophosphate
47341-71-9
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010901Subventions
Organisme : Wellcome Trust
ID : FC001189
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204909/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1202/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001189
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI123457
Pays : United States
Organisme : Cancer Research UK
ID : FC001189
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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