PXD030057

PXD030057 is an original dataset announced via ProteomeXchange.

Title	A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signaling in Toxoplasma gondii.
Description	Fundamental processes of obligate intracellular parasites, such as Plasmodium falciparum and Toxoplasma gondii are controlled by a set of plant-like calcium dependent kinases (CDPKs), the conserved cAMP- and cGMP-dependent protein kinases (PKA and PKG), second messengers and lipid signalling. While some major components of the signalling networks have been identified, how these are connected is largely not known. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels to activate PKG or CDPKs, respectively. We show that both these inducers trigger near identical signalling pathways and provide evidence for a feedback loop involving CDPK3. We measure phospho- and lipid signalling in parasites treated with the Ca2+ ionophore A23187 in a sub-minute timecourse and show CDPK3-dependent regulation of diacylglycerol levels and increased phosphorylation of four phosphodiesterases (PDEs), suggesting their function in the feedback loop. Disruption of CDPK3 leads to elevated cAMP levels and inhibition of PKA signalling rescues the egress defect of ΔCDPK3 parasites treated with A23187. Biochemical analysis of the four PDEs identifies PDE2 as the only cAMP-specific PDE among these candidates while the other PDEs are cGMP specific; two of which are inhibited by the predicted PDE inhibitor BIPPO. Conditional deletion of the 4 PDEs supports an important, but non-essential role of PDE1 and PDE2 for growth, while only the latter plays a role in controlling A23187-mediated egress. In summary, we uncover a positive feedback loop that potentiates signalling during egress and links several signalling pathways together.
HostingRepository	PRIDE
AnnounceDate	2022-10-17
AnnouncementXML	Submission_2022-10-17_02:02:13.222.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MalgorzataBroncel
SpeciesList	scientific name: Toxoplasma gondii RH; NCBI TaxID: 383379; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-30 07:50:16	ID requested
⏵ 1	2022-10-17 02:02:13	announced

Dataset with its publication pending

submitter keyword: Toxoplasma gondii, Calcium-signalling, egress, CDPK3

MoritzTreeck
contact affiliation	The Francis Crick Institute Signalling in Apicomplexan Parasites Laboratory London NW1 1AT United Kingdom
contact email	moritz.treeck@crick.ac.uk
lab head
MalgorzataBroncel
contact affiliation	The Francis Crick Institute
contact email	malgorzata.broncel@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030057
     1. Label: PRIDE project
     2. Name: A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signaling in Toxoplasma gondii.