Characterization of the ATP4 ion pump in Toxoplasma gondii
- Author(s)
- Lehane, AM; Dennis, ASM; Bray, KO; Li, D; Rajendran, E; Mccoy, JM; McArthur, HM; Winterberg, M; Rahimi, F; Tonkin, CJ; Kirk, K; van Dooren, GG;
- Details
- Publication Year 2019-02-05,Volume 294,Issue #14,Page 5720-5734
- Journal Title
- Journal of Biological Chemistry
- Publication Type
- Journal Article
- Abstract
- The Plasmodium falciparum ATPase PfATP4 is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca(2+) transporter, but recent evidence suggests that it is a Na(+) efflux pump, extruding Na(+) in exchange for H(+) Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca(2+), but rendered parasites unable to regulate their cytosolic Na(+) concentration ([Na(+)]cyt). PfATP4 inhibitors caused an increase in [Na(+)]cyt and a cytosolic alkalinization in wild type, but not in TgATP4-knockdown, parasites. Parasites in which TgATP4 was knocked down or disrupted exhibited a growth defect, attributable to a reduced viability of extracellular parasites. Parasites in which TgATP4 had been disrupted showed reduced virulence in mice. These results provide evidence for ATP4 proteins playing a key, conserved role in Na(+) regulation in apicomplexan parasites.
- Publisher
- ASBMB
- Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- 30723156
- Publisher's Version
- https://doi.org/10.1074/jbc.RA118.006706
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-03-13 08:04:17
Last Modified: 2020-02-05 12:57:13