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Genome-wide Functional Analysis of Plasmodium Protein Phosphatases Reveals Key Regulators of Parasite Development and Differentiation

Guttery, David S.; TEWARI, RITA; Poulin, Benoit; Ramaprasad, Abhinay; Wall, Richard J.; Ferguson, David J.P.; Brady, Declan; Patzewitz, Eva-Maria; Whipple, Sarah; Straschil, Ursula; Wright, Megan H.; Mohamed, Alyaa M.A.H.; Radhakrishnan, Anand; Arold, Stefan T.; Tate, Edward W.; Holder, Anthony A.; Wickstead, Bill; Pain, Arnab


David S. Guttery

Professor of Parasite Cell Biology

Benoit Poulin

Abhinay Ramaprasad

Richard J. Wall

David J.P. Ferguson

Declan Brady

Eva-Maria Patzewitz

Sarah Whipple

Ursula Straschil

Megan H. Wright

Alyaa M.A.H. Mohamed

Anand Radhakrishnan

Stefan T. Arold

Edward W. Tate

Anthony A. Holder

Arnab Pain


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. © 2014 The Authors.


Guttery, D. S., TEWARI, R., Poulin, B., Ramaprasad, A., Wall, R. J., Ferguson, D. J., …Pain, A. (2014). Genome-wide Functional Analysis of Plasmodium Protein Phosphatases Reveals Key Regulators of Parasite Development and Differentiation. Cell Host and Microbe, 16(1), 128-140.

Journal Article Type Article
Acceptance Date May 27, 2014
Online Publication Date Jul 9, 2014
Publication Date Jul 9, 2014
Deposit Date May 17, 2018
Publicly Available Date Aug 12, 2020
Journal Cell Host and Microbe
Print ISSN 1931-3128
Electronic ISSN 1934-6069
Publisher Elsevier (Cell Press)
Peer Reviewed Peer Reviewed
Volume 16
Issue 1
Pages 128-140
Public URL
Publisher URL


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