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PXD009157

PXD009157 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhosphodiesterase beta controls cAMP signalling during malaria parasite erythrocyte invasion
DescriptionCyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Specific phosphodiesterase (PDE) enzymes are known to control cGMP levels in the parasite, but the mechanisms by with cAMP is regulated remain enigmatic. Here we show that P. falciparum PDEbeta translocates via the ER to an apical location and finally to the plasma membrane of merozoites within the segmented schizont. PDEbeta is essential for blood stage replication, with conditional gene disruption causing a profound invasion phenotype and rapid death of those merozoites that are able to invade a host erythrocyte. Importantly we also demonstrate that PDEbeta is able to hydrolyse both cAMP and cGMP. Loss of PDEbeta activity results in significantly elevated levels of cAMP which correlate temporally with the observed reduction in merozoite invasion. Quantitative phosphoproteomic analysis revealed a >2-fold increase in phosphorylation for >250 phosphosites following silencing of PfPDEbeta. These included a highly significant increase in phosphorylation at PKA substrate consensus sequences. Our results suggest that dysregulated phosphorylation of MyoA S19 and AMA1 S610 likely contributes to the PfPDEbeta knockout invasion phenotype, that PKG activity governs cAMP levels and PKA activation prior to merozoite egress, and that PfPDEbeta has an essential function in regulation cAMP levels in early intra-erythrocytic development in P. falciparum.
HostingRepositoryPRIDE
AnnounceDate2019-02-27
AnnouncementXMLSubmission_2019-02-27_02:15:31.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndrew Jones
SpeciesList scientific name: Plasmodium falciparum Mad71/Papua New Guinea; NCBI TaxID: 70154; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-03-09 03:41:39ID requested
12019-02-27 02:15:32announced
Publication List
Flueck C, Drought LG, Jones A, Patel A, Perrin AJ, Walker EM, Nofal SD, Snijders AP, Blackman MJ, Baker DA, Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion. PLoS Biol, 17(2):e3000154(2019) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Malaria, PKA, Phosphoproteomics, Orbitrap, cAMP, TMT
Contact List
Bram Snijders
contact affiliationMass Spectrometry Proteomics Science Technology Platform, The Francis Crick Institute, London, UK
contact emailBram.Snijders@crick.ac.uk
lab head
Andrew Jones
contact affiliationThe Francis Crick Institute
contact emailAndrew.Jones@crick.ac.uk
dataset submitter
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