UNIGE document Scientific Article
previous document  unige:28791  next document
add to browser collection
Title

The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development

Authors
Guttery, David S
Pittman, Jon K
Poulin, Benoit
McFarlane, Leon R
Slavic, Ksenija
Wheatley, Sally P
show hidden authors show all authors [1 - 11]
Published in PLOS Pathogens. 2013, vol. 9, no. 2, p. e1003191
Abstract Ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due to its varied and essential roles, free Ca(2+) is tightly regulated by complex mechanisms. These mechanisms are therefore of interest as putative drug targets. One pathway in Ca(2+) homeostatic control in apicomplexans uses a Ca(2+)/H(+) exchanger (a member of the cation exchanger family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised in asexual blood stage parasites. To determine the physiological importance of apicomplexan CAXs, tagging and knock-out strategies were undertaken in the genetically tractable T. gondii and P. berghei parasites. In addition, a yeast heterologous expression system was used to study the function of apicomplexan CAXs. Tagging of T. gondii and P. berghei CAXs (TgCAX and PbCAX) under control of their endogenous promoters could not demonstrate measureable expression of either CAX in tachyzoites and asexual blood stages, respectively. These results were consistent with the ability of parasites to tolerate knock-outs of the genes for TgCAX and PbCAX at these developmental stages. In contrast, PbCAX expression was detectable during sexual stages of development in female gametocytes/gametes, zygotes and ookinetes, where it was dispersed in membranous networks within the cytosol (with minimal mitochondrial localisation). Furthermore, genetically disrupted parasites failed to develop further from "round" form zygotes, suggesting that PbCAX is essential for ookinete development and differentiation. This impeded phenotype could be rescued by removal of extracellular Ca(2+). Therefore, PbCAX provides a mechanism for free living parasites to multiply within the ionic microenvironment of the mosquito midgut. Ca(2+) homeostasis mediated by PbCAX is critical and suggests plasmodial CAXs may be targeted in approaches designed to block parasite transmission.
Identifiers
PMID: 23468629
Full text
Article (Published version) (3.4 MB) - public document Free access
Structures
Research group Biologie d'un parasite intracellulaire obligatoire (773)
Citation
(ISO format)
GUTTERY, David S et al. The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development. In: PLOS Pathogens, 2013, vol. 9, n° 2, p. e1003191. https://archive-ouverte.unige.ch/unige:28791

232 hits

277 downloads

Update

Deposited on : 2013-07-05

Export document
Format :
Citation style :