The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

Rita Tewari; Ursula Straschil; Alex Bateman; Ulrike Böhme; Inna Cherevach; Peng Gong; Arnab Pain; Oliver Billker

doi:10.1016/j.chom.2010.09.006

The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

Rita Tewari, Ursula Straschil, Alex Bateman, Ulrike Böhme, Inna Cherevach, Peng Gong, Arnab Pain, Oliver Billker

Research output: Contribution to journal › Article › peer-review

222 Scopus citations

Abstract

Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

Original language	English (US)
Pages (from-to)	377-387
Number of pages	11
Journal	Cell Host & Microbe
Volume	8
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2010.09.006
State	Published - Oct 21 2010

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01

ASJC Scopus subject areas

Molecular Biology
Cancer Research
General Immunology and Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2010.09.006

https://repository.kaust.edu.sa/bitstream/10754/334569/1/Article-Cell_Host_-The_system-2010.pdf

Cite this

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title = "The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission",

abstract = "Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.",

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AU - Straschil, Ursula

AU - Bateman, Alex

AU - Böhme, Ulrike

AU - Cherevach, Inna

AU - Gong, Peng

AU - Pain, Arnab

AU - Billker, Oliver

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AB - Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

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The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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