ArticlePLoS pathogens2020
Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Article
- Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Nutrient stress dramatically increases malaria parasite clag2 copy number to increase host cell permeability and enable pathogen survival.PLoS pathogens · 2025Article
- The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels.Cell chemical biology · 2025Article
- A High-Throughput Inhibitor Screen Targeting CLAG3 Export and Membrane Insertion on Human Erythrocytes Infected with Malaria Parasites.Pathogens (Basel, Switzerland) · 2025Article
- Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum.Journal of biomedical science · 2025Article
- Guanidinium Chloride-Induced Haemolysis Assay to Measure New Permeation Pathway Functionality in Rodent MalariaBiomolecules · 2024Article
- Article
- Novel Ion Channel Genes in Malaria Parasites.Genes · 2024Review
- Critical interdependencies between Plasmodium nutrient flux and drugs.Trends in parasitology · 2023Review
- Unique Properties of Nutrient Channels onPathogens (Basel, Switzerland) · 2023Review
- Knock-sideways by inducible ER retrieval enables a unique approach for studyingProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Roles of the RON3 C-terminal fragment in erythrocyte invasion and blood-stage parasite proliferation inFrontiers in cellular and infection microbiology · 2023Article
- Down the membrane hole: Ion channels in protozoan parasites.PLoS pathogens · 2022Review
- Epigenetics of malaria parasite nutrient uptake, but why?Trends in parasitology · 2022Review
- Article
- RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes.Communications biology · 2022Article
- A toolbox for conditional control of gene expression in apicomplexan parasites.Molecular microbiology · 2022Review
- Labeling Strategies for Surface-Exposed Protein Visualization and Determination inFrontiers in cellular and infection microbiology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Malaria parasites activate a broad-selectivity ion channel on their host erythrocyte membrane to obtain essential nutrients from the bloodstream. This conserved channel, known as the plasmodial surface anion channel (PSAC), has been linked to parasite clag3 genes in P. falciparum, but epigenetic switching between the two copies of this gene hinders clear understanding of how the encoded protein determines PSAC activity. Here, we used linkage analysis in a P. falciparum cross where one parent carries a single clag3 gene to overcome the effects of switching and confirm a primary role of the clag3 product with high confidence. Despite Mendelian inheritance, CLAG3 conditional knockdown revealed remarkably preserved nutrient and solute uptake. Even more surprisingly, transport remained sensitive to a CLAG3 isoform-specific inhibitor despite quantitative knockdown, indicating that low doses of the CLAG3 transgene are sufficient to confer block. We then produced a complete CLAG3 knockout line and found it exhibits an incomplete loss of transport activity, in contrast to rhoph2 and rhoph3, two PSAC-associated genes that cannot be disrupted because nutrient uptake is abolished in their absence. Although the CLAG3 knockout did not incur a fitness cost under standard nutrient-rich culture conditions, this parasite could not be propagated in a modified medium that more closely resembles human plasma. These studies implicate oligomerization of CLAG paralogs encoded by various chromosomes in channel formation. They also reveal that CLAG3 is dispensable under standard in vitro conditions but required for propagation under physiological conditions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.