학술논문

Plasmodium falciparum formins are essential for invasion and sexual stage development.
Document Type
Article
Source
Communications Biology. 8/18/2023, Vol. 6 Issue 1, p1-15. 15p.
Subject
*FORMINS
*PLASMODIUM falciparum
*SMALL molecules
*PLASMODIUM
*GENETIC regulation
Language
ISSN
2399-3642
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. The Plasmodium falciparum formin proteins FRM1 and FRM2, have distinct cellular locations and are essential for asexual and sexual blood stage development respectively. [ABSTRACT FROM AUTHOR]