Plasmodium falciparum formins are essential for invasion and sexual stage development
- Author(s)
- Collier, S; Pietsch, E; Dans, M; Ling, D; Tavella, TA; Lopaticki, S; Marapana, DS; Shibu, MA; Andrew, D; Tiash, S; McMillan, PJ; Gilson, P; Tilley, L; Dixon, MWA;
- Details
- Publication Year 2023-08-18,Volume 6,Issue #1,Page 861
- Journal Title
- Communications Biology
- Abstract
- The malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including intracellular trafficking, gene regulation, parasite motility and invasion. In this work we assign functions to the Plasmodium falciparum formins 1 and 2 (FRM1 and FRM2) proteins in asexual and sexual blood stage development. We show that FRM1 is essential for merozoite invasion and FRM2 is required for efficient cell division. We also observed divergent functions for FRM1 and FRM2 in gametocyte development. Conditional deletion of FRM1 leads to a delay in gametocyte stage progression. We show that FRM2 controls the actin and microtubule cytoskeletons in developing gametocytes, with premature removal of the protein resulting in a loss of transmissible stage V gametocytes. Lastly, we show that targeting formin proteins with the small molecule inhibitor of formin homology domain 2 (SMIFH2) leads to a multistage block in asexual and sexual stage parasite development.
- Publisher
- NPG
- Keywords
- *Actins/genetics; Formins; *Plasmodium falciparum/genetics; Cell Division; Cytoskeleton
- Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- 37596377
- Publisher's Version
- https://doi.org/10.1038/s42003-023-05233-y
- Open Access at Publisher's Site
https://doi.org/10.1038/s42003-023-05233-y.- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-08-28 09:37:11
Last Modified: 2023-08-28 09:46:19