Basigin mediation of Plasmodium falciparum red blood cell invasion does not require its transmembrane domain or interaction with monocarboxylate transporter 1

King, Nadine R.; Freire, Catarina Martins; Touhami, Jawida; Sitbon, Marc; Toye, Ashley M.; Satchwell, Timothy J.

Abstract

Plasmodium falciparum invasion of the red blood cell is reliant upon the essential interaction of PfRh5 with the host receptor protein basigin. Basigin exists as part of one or more multiprotein complexes, most notably through interaction with the monocarboxylate transporter MCT1. However, the potential requirement for basigin association with MCT1 and the wider role of basigin host membrane context and lateral protein associations during merozoite invasion has not been established. Using genetically manipulated in vitro derived reticulocytes, we demonstrate the ability to uncouple basigin ectodomain presentation from its transmembrane domain-mediated interactions, including with MCT1. Merozoite invasion of reticulocytes is unaffected by disruption of basigin-MCT1 interaction and by removal or replacement of the basigin transmembrane helix. Therefore, presentation of the basigin ectodomain at the red blood cell surface, independent of its native association with MCT1 or other interactions mediated by the transmembrane domain, is sufficient to facilitate merozoite invasion.

• Journal Article Type: Article
• Acceptance Date: Jan 19, 2024
• Online Publication Date: Feb 5, 2024
• Publication Date: Feb 5, 2024
• Deposit Date: Jul 11, 2024
• Publicly Available Date: Jul 12, 2024
• Journal: PLoS Pathogens
• Print ISSN: 1553-7366
• Electronic ISSN: 1553-7374
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 2
• Article Number: e1011989
• DOI: https://doi.org/10.1371/journal.ppat.1011989
• Public URL: https://uwe-repository.worktribe.com/output/12120144