TY - JOUR
T1 - The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission
AU - Tewari, Rita
AU - Straschil, Ursula
AU - Bateman, Alex
AU - Böhme, Ulrike
AU - Cherevach, Inna
AU - Gong, Peng
AU - Pain, Arnab
AU - Billker, Oliver
N1 - KAUST Repository Item: Exported on 2020-10-01
PY - 2010/10/21
Y1 - 2010/10/21
N2 - 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.
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.
UR - http://hdl.handle.net/10754/334569
UR - https://linkinghub.elsevier.com/retrieve/pii/S1931312810003082
UR - http://www.scopus.com/inward/record.url?scp=77958094517&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2010.09.006
DO - 10.1016/j.chom.2010.09.006
M3 - Article
C2 - 20951971
VL - 8
SP - 377
EP - 387
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 4
ER -
