Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization.

Abstract

Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes.

• Authors: Sudhir Kumar, Clari Valansi, Meseret T Haile, Xiaohui Li, Kateryna Flyak, Abhisek Dwivedy, Biley A Abatiyow, Amanda S Leeb, Spencer Y Kennedy, Nelly M Camargo, Ashley M Vaughan, Nicolas G Brukman, Benjamin Podbilewicz, Stefan H I Kappe
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 79 Issue 11 Pg. 549 (Oct 14 2022) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 36241929 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Topics

• Animals
• Cell Membrane
• Female
• Fertilization
• Germ Cells (metabolism)
• Humans
• Malaria
• Male
• Parasites
• Plasmodium falciparum (genetics)