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

David S. Guttery, 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. Abdel-Haleem, Anand Radhakrishnan, Stefan T. Arold, Edward W. Tate, Anthony A. Holder, Bill Wickstead, Arnab Pain, Rita Tewari

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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. © 2014 The Authors.
Original languageEnglish (US)
Pages (from-to)128-140
Number of pages13
JournalCell Host & Microbe
Volume16
Issue number1
DOIs
StatePublished - Jul 9 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Immunology and Microbiology(all)

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