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Genome-wide Functional Analysis of Plasmodium Protein Phosphatases Reveals Key Regulators of Parasite Development and Differentiation
journal contribution
posted on 2016-02-23, 14:30 authored by David Stephen Guttery, B. Poulin, A. Ramaprasad, R. J. Wall, D. J. P. Ferguson, D. Brady, E-M. Patzewitz, B. S. Whipple, U. Straschil, M. H. Wright, A. M. A. H. Mohamed, A. Radhakrishnan, S. T. Arold, E. W. Tate, A. A. Holder, B. Wickstead, A. Pain, R. TewariReversible 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.
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Citation
Cell Host & Microbe, 2014, 16(1), pp. 128-140Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular MedicineVersion
- VoR (Version of Record)
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Cell Host & MicrobePublisher
Elsevier (Cell Press)issn
1931-3128eissn
1934-6069Acceptance date
2014-05-27Copyright date
2014Available date
2016-02-23Publisher DOI
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http://www.sciencedirect.com/science/article/pii/S1931312814002194Language
enAdministrator link
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