Genome-wide Functional Analysis of Plasmodium Protein Phosphatases Reveals Key Regulators of Parasite Development and Differentiation
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Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2014-07-09
Date Acceptance
2014-05-27
Citation
Cell Host & Microbe, 2014, 16 (1), pp.128-140
ISSN
1934-6069
Publisher
Elsevier (Cell Press)
Start Page
128
End Page
140
Journal / Book Title
Cell Host & Microbe
Volume
16
Issue
1
Copyright Statement
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
MALARIA PARASITE
LIFE-CYCLE
TYROSINE-PHOSPHATASE
PROTEOMIC ANALYSES
GLIDING MOTILITY
MOSQUITO MIDGUT
SEX-RATIO
FALCIPARUM
INVASION
KINASE
Publication Status
Published