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Cell Host Microbe. 2014 Jul 9;16(1):128-40. doi: 10.1016/j.chom.2014.05.020.

Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.

Author information

1
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
2
Computational Bioscience Research Center (CBRC), Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
3
Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
4
Division of Cell and Molecular Biology, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
5
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
6
Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. Electronic address: aholder@nimr.mrc.ac.uk.
7
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK. Electronic address: rita.tewari@nottingham.ac.uk.

Abstract

Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria.

PMID:
25011111
PMCID:
PMC4094981
DOI:
10.1016/j.chom.2014.05.020
[Indexed for MEDLINE]
Free PMC Article

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