Version 1
: Received: 19 April 2024 / Approved: 23 April 2024 / Online: 23 April 2024 (11:57:51 CEST)
How to cite:
Gupta, A.; Gonzalez-Chavez, Z.; Desai, S.A. Partially Overlapping Contributions of Clag Paralogs to Nutrient Uptake Channels in P. falciparum. Preprints2024, 2024041487. https://doi.org/10.20944/preprints202404.1487.v1
Gupta, A.; Gonzalez-Chavez, Z.; Desai, S.A. Partially Overlapping Contributions of Clag Paralogs to Nutrient Uptake Channels in P. falciparum. Preprints 2024, 2024041487. https://doi.org/10.20944/preprints202404.1487.v1
Gupta, A.; Gonzalez-Chavez, Z.; Desai, S.A. Partially Overlapping Contributions of Clag Paralogs to Nutrient Uptake Channels in P. falciparum. Preprints2024, 2024041487. https://doi.org/10.20944/preprints202404.1487.v1
APA Style
Gupta, A., Gonzalez-Chavez, Z., & Desai, S.A. (2024). Partially Overlapping Contributions of Clag Paralogs to Nutrient Uptake Channels in <em>P</em>. <em>falciparum</em>. Preprints. https://doi.org/10.20944/preprints202404.1487.v1
Chicago/Turabian Style
Gupta, A., Zabdi Gonzalez-Chavez and Sanjay A. Desai. 2024 "Partially Overlapping Contributions of Clag Paralogs to Nutrient Uptake Channels in <em>P</em>. <em>falciparum</em>" Preprints. https://doi.org/10.20944/preprints202404.1487.v1
Abstract
Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.
Keywords
Plasmodium falciparum; malaria; multigene family; CLAG; nutrient uptake; ion channel; DNA transfection
Subject
Biology and Life Sciences, Parasitology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
