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

Handle URI:
http://hdl.handle.net/10754/334569
Title:
The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission
Authors:
Tewari, Rita; Straschil, Ursula; Bateman, Alex; Böhme, Ulrike; Cherevach, Inna; Gong, Peng; Pain, Arnab ( 0000-0002-1755-2819 ) ; Billker, Oliver
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.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Tewari R, Straschil U, Bateman A, Böhme U, Cherevach I, et al. (2010) The Systematic Functional Analysis of Plasmodium Protein Kinases Identifies Essential Regulators of Mosquito Transmission. Cell Host and Microbe 8: 377-387. doi:10.1016/j.chom.2010.09.006.
Publisher:
Cell Press
Journal:
Cell Host and Microbe
Issue Date:
21-Oct-2010
DOI:
10.1016/j.chom.2010.09.006
PubMed ID:
20951971
PubMed Central ID:
PMC2977076
Type:
Article
ISSN:
19313128
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorTewari, Ritaen
dc.contributor.authorStraschil, Ursulaen
dc.contributor.authorBateman, Alexen
dc.contributor.authorBöhme, Ulrikeen
dc.contributor.authorCherevach, Innaen
dc.contributor.authorGong, Pengen
dc.contributor.authorPain, Arnaben
dc.contributor.authorBillker, Oliveren
dc.date.accessioned2014-11-11T14:30:01Z-
dc.date.available2014-11-11T14:30:01Z-
dc.date.issued2010-10-21en
dc.identifier.citationTewari R, Straschil U, Bateman A, Böhme U, Cherevach I, et al. (2010) The Systematic Functional Analysis of Plasmodium Protein Kinases Identifies Essential Regulators of Mosquito Transmission. Cell Host and Microbe 8: 377-387. doi:10.1016/j.chom.2010.09.006.en
dc.identifier.issn19313128en
dc.identifier.pmid20951971en
dc.identifier.doi10.1016/j.chom.2010.09.006en
dc.identifier.urihttp://hdl.handle.net/10754/334569en
dc.description.abstractAlthough 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.en
dc.language.isoenen
dc.publisherCell Pressen
dc.rightsOpen Access funded by Wellcome Trusten
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en
dc.subjectclathrinen
dc.subjectprotein kinaseen
dc.subjectenergy metabolismen
dc.subjectmosquitoen
dc.subjectnonhumanen
dc.subjectparasite developmenten
dc.subjectphenotypeen
dc.subjectPlasmodium falciparumen
dc.subjectpriority journalen
dc.subjectprotein structureen
dc.subjectsalivary glanden
dc.subjectsexual developmenten
dc.subjectsporozoiteen
dc.subjectzygoteen
dc.subjectAmino Acid Sequenceen
dc.subjectAnimalsen
dc.subjectAnophelesen
dc.subjectEnergy Metabolismen
dc.subjectFemaleen
dc.subjectGene Deletionen
dc.subjectGene Knockout Techniquesen
dc.subjectInsect Vectorsen
dc.subjectLife Cycle Stagesen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Inbred BALB Cen
dc.subjectMolecular Sequence Dataen
dc.subjectMutationen
dc.subjectPlasmodium bergheien
dc.subjectPlasmodium falciparumen
dc.subjectProtein Kinasesen
dc.subjectProtozoan Proteinsen
dc.subjectSporozoitesen
dc.subjectAnopheles stephensien
dc.subjectEukaryotaen
dc.subjectMammaliaen
dc.subjectMusen
dc.subjectPlasmodium (Apicomplexa)en
dc.subjectPlasmodium bergheien
dc.subjectPlasmodium falciparumen
dc.subjectRodentiaen
dc.titleThe systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmissionen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalCell Host and Microbeen
dc.identifier.pmcidPMC2977076en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionInstitute of Genetics, QMC, University of Nottingham, Nottingham NG7 2UH, United Kingdomen
dc.contributor.institutionDivision of Cell and Molecular Biology, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdomen
dc.contributor.institutionWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdomen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorPain, Arnaben

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