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 journalArticlepeer-review

169 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 languageEnglish (US)
Pages (from-to)377-387
Number of pages11
JournalCell Host & Microbe
Volume8
Issue number4
DOIs
StatePublished - Oct 21 2010

ASJC Scopus subject areas

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

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