title: Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.
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.
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Guttery
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Benoit
authors.initials: B
authors.lastname: Poulin
authors.affiliation: 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.
authors.forename: Abhinay
authors.initials: A
authors.lastname: Ramaprasad
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wall
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Declan
authors.initials: D
authors.lastname: Brady
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Patzewitz
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whipple
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Ursula
authors.initials: U
authors.lastname: Straschil
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Megan H
authors.initials: MH
authors.lastname: Wright
authors.affiliation: 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.
authors.forename: Alyaa M A H
authors.initials: AM
authors.lastname: Mohamed
authors.affiliation: 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.
authors.forename: Anand
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: 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.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. Electronic address: aholder@nimr.mrc.ac.uk.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Bill
authors.initials: B
authors.lastname: Wickstead
authors.affiliation: 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.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: 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.
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D010962:Plasmodium berghei / Q000201:enzymology* / Q000254:growth & development*; D010963:Plasmodium falciparum / Q000201:enzymology
chemical_list: D010749:Phosphoprotein Phosphatases