TY - JOUR
T1 - Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation
AU - Guttery, David S.
AU - Poulin, Benoit
AU - Ramaprasad, Abhinay
AU - Wall, Richard J.
AU - Ferguson, David J.P.
AU - Brady, Declan
AU - Patzewitz, Eva Maria
AU - Whipple, Sarah
AU - Straschil, Ursula
AU - Wright, Megan H.
AU - Mohamed, Alyaa M.A.H.
AU - Radhakrishnan, Anand
AU - Arold, Stefan T.
AU - Tate, Edward W.
AU - Holder, Anthony A.
AU - Wickstead, Bill
AU - Pain, Arnab
AU - Tewari, Rita
N1 - Funding Information:
The project is funded by MRC Investigator Award and MRC project grants to R.T. (G0900109, G0900278, and MR/K011782/1); A.A.H. is funded by the MRC (U117532067 and G0900278) and the EU, FP7 grant agreement 242095 (EviMalar); D.J.P.F. is funded by a Wellcome Trust Equipment Grant; E.W.T. is funded by the MRC (G0900278); B.W. is funded by a BBSRC new investigator research grant (BB/J01477X/1). A.P., A. Ramaprasad, A.M.A.H.M., A. Radhakrishnan, and S.T.A. are funded by KAUST; M.H.W. is funded by the EPSRC. We would like to thank Nigel Halliday, Balázs Szöőr, Sara Sandrini, Peng Gong, and Julie Rodgers for their discussions and assistance.
PY - 2014/7/9
Y1 - 2014/7/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84904203338
UR - https://www.scopus.com/pages/publications/84904203338#tab=citedBy
U2 - 10.1016/j.chom.2014.05.020
DO - 10.1016/j.chom.2014.05.020
M3 - Article
C2 - 25011111
AN - SCOPUS:84904203338
SN - 1931-3128
VL - 16
SP - 128
EP - 140
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -