ArticleMolecular pharmacology2012
Solute restriction reveals an essential role for clag3-associated channels in malaria parasite nutrient acquisition.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 87 citations in OpenAlex.
- Physiological febrile heat stress increases cytoadhesion through increased protein trafficking ofeLife · 2026Article
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- 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
- The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound.Nature microbiology · 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
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- 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
- Cultivation of Asexual Intraerythrocytic Stages ofPathogens (Basel, Switzerland) · 2023Review
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- Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes.Microbiology spectrum · 2023Article
- Review
- Optimized Pyridazinone Nutrient Channel Inhibitors Are Potent and Specific Antimalarial Leads.Molecular pharmacology · 2022Article
- Epigenetics of malaria parasite nutrient uptake, but why?Trends in parasitology · 2022Review
- Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The plasmodial surface anion channel (PSAC) increases erythrocyte permeability to many solutes in malaria but has uncertain physiological significance. We used a PSAC inhibitor with different efficacies against channels from two Plasmodium falciparum parasite lines and found concordant effects on transport and in vitro parasite growth when external nutrient concentrations were reduced. Linkage analysis using this growth inhibition phenotype in the Dd2 × HB3 genetic cross mapped the clag3 genomic locus, consistent with a role for two clag3 genes in PSAC-mediated transport. Altered inhibitor efficacy, achieved through allelic exchange or expression switching between the clag3 genes, indicated that the inhibitor kills parasites through direct action on PSAC. In a parasite unable to undergo expression switching, the inhibitor selected for ectopic homologous recombination between the clag3 genes to increase the diversity of available channel isoforms. Broad-spectrum inhibitors, which presumably interact with conserved sites on the channel, also exhibited improved efficacy with nutrient restriction. These findings indicate that PSAC functions in nutrient acquisition for intracellular parasites. Although key questions regarding the channel and its biological role remain, antimalarial drug development targeting PSAC should be pursued.
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