PXD009157-1

PXD009157 is an original dataset announced via ProteomeXchange.

Title	Phosphodiesterase beta controls cAMP signalling during malaria parasite erythrocyte invasion
Description	Cyclic 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.
HostingRepository	PRIDE
AnnounceDate	2019-02-27
AnnouncementXML	Submission_2019-02-27_02:15:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Jones
SpeciesList	scientific name: Plasmodium falciparum Mad71/Papua New Guinea; NCBI TaxID: 70154; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-09 03:41:39	ID requested
⏵ 1	2019-02-27 02:15:32	announced

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]

curator keyword: Biological

submitter keyword: Malaria, PKA, Phosphoproteomics, Orbitrap, cAMP, TMT

Bram Snijders
contact affiliation	Mass Spectrometry Proteomics Science Technology Platform, The Francis Crick Institute, London, UK
contact email	Bram.Snijders@crick.ac.uk
lab head
Andrew Jones
contact affiliation	The Francis Crick Institute
contact email	Andrew.Jones@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009157
     1. Label: PRIDE project
     2. Name: Phosphodiesterase beta controls cAMP signalling during malaria parasite erythrocyte invasion