ArticlePLoS biology2019
Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Phosphorylation in theJournal of proteome research · 2024Pooled it
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- An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP.Science advances · 2025Article
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- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
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- Red blood cell signaling is functionally conserved iniScience · 2024Article
- Generation of a new DiCre expressing parasite strain for functional characterization of Plasmodium falciparum genes in blood stages.Scientific reports · 2024Article
- Orthologs ofMicrobiology spectrum · 2024Article
- SPARK regulates AGC kinases central to theeLife · 2024Article
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- Long non-coding RNAs are essential for Schistosoma mansoni pairing-dependent adult worm homeostasis and fertility.PLoS pathogens · 2023Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Exploring Potential Antimalarial Candidate from Medicinal Plants of Kheaw Hom Remedy.Tropical medicine and infectious disease · 2022Article
- A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.PLoS pathogens · 2022Article
- A toolbox for conditional control of gene expression in apicomplexan parasites.Molecular microbiology · 2022Review
- Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites.mSphere · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Phosphodiesterase (PDE) enzymes are known to control cyclic GMP (cGMP) levels in the parasite, but the mechanisms by which cyclic AMP (cAMP) is regulated remain enigmatic. Here, we demonstrate that Plasmodium falciparum phosphodiesterase β (PDEβ) hydrolyses both cAMP and cGMP and is essential for blood stage viability. Conditional gene disruption causes a profound reduction in invasion of erythrocytes and rapid death of those merozoites that invade. We show that this dual phenotype results from elevated cAMP levels and hyperactivation of the cAMP-dependent protein kinase (PKA). Phosphoproteomic analysis of PDEβ-null parasites reveals a >2-fold increase in phosphorylation at over 200 phosphosites, more than half of which conform to a PKA substrate consensus sequence. We conclude that PDEβ plays a critical role in governing correct temporal activation of PKA required for erythrocyte invasion, whilst suppressing untimely PKA activation during early intra-erythrocytic development.
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