The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.
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.
Institute of Genetics, QMC, University of Nottingham, Nottingham NG7 2UH, UK. rita.tewari@nottingham.ac.uk
Rita
R
Tewari
Ursula
U
Straschil
Alex
A
Bateman
Ulrike
U
Böhme
Inna
I
Cherevach
Peng
P
Gong
Arnab
A
Pain
Oliver
O
Billker
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D007303:Insect Vectors / Q000469:parasitology; D008018:Life Cycle Stages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010962:Plasmodium berghei / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D011494:Protein Kinases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism
D015800:Protozoan Proteins; D011494:Protein Kinases