ArticlePLoS pathogens2014
The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 96 citations in OpenAlex.
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- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
- Red blood cell signaling is functionally conserved iniScience · 2024Article
- Orthologs ofMicrobiology spectrum · 2024Article
- RNA polymerase III is involved in regulatingeLife · 2024Article
- Review
- Coordination of apicoplast transcription in a malaria parasite by internal and host cues.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites.mSphere · 2022Article
- Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic ProtozoaInternational journal of molecular sciences · 2021Review
- Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes.Molecular microbiology · 2021Review
- Calcium in the Backstage of Malaria Parasite Biology.Frontiers in cellular and infection microbiology · 2021Review
- cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition ofFrontiers in microbiology · 2021Review
- An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Article
- Article
- The protozoan parasiteComputational and structural biotechnology journal · 2020Article
- Uncovering the Cyclic AMP Signaling Pathway of the Protozoan ParasiteFrontiers in cellular and infection microbiology · 2020Article
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify cAMP as a key regulator that triggers the timely secretion of microneme proteins enabling receptor-engagement and invasion. We demonstrate that exposure of merozoites to a low K+ environment, typical of blood plasma, activates a bicarbonate-sensitive cytoplasmic adenylyl cyclase to raise cytosolic cAMP levels and activate protein kinase A, which regulates microneme secretion. We also show that cAMP regulates merozoite cytosolic Ca2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca2+ are essential to trigger microneme secretion. Our identification of the different elements in cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides novel targets to inhibit blood stage parasite growth and prevent malaria.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.