title: The Plasmodium eukaryotic initiation factor-2alpha kinase IK2 controls the latency of sporozoites in the mosquito salivary glands.
abstract: Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2alpha (eIF2alpha) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2alpha phosphatase removes the PO4 from eIF2alpha-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2alpha is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells.
authors.affiliation: Michael Heidelberger Division, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Clare
authors.initials: C
authors.lastname: Fennell
authors.forename: Lisa
authors.initials: L
authors.lastname: Ranford-Cartwright
authors.forename: Ramanavelan
authors.initials: R
authors.lastname: Sakthivel
authors.forename: Pascale
authors.initials: P
authors.lastname: Gueirard
authors.forename: Stephan
authors.initials: S
authors.lastname: Meister
authors.forename: Anat
authors.initials: A
authors.lastname: Caspi
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: Renu
authors.initials: R
authors.lastname: Tuteja
authors.forename: William J
authors.initials: WJ
authors.lastname: Sullivan
authors.forename: David S
authors.initials: DS
authors.lastname: Roos
authors.forename: Beatriz M A
authors.initials: BM
authors.lastname: Fontoura
authors.forename: Robert
authors.initials: R
authors.lastname: Ménard
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
authors.forename: Victor
authors.initials: V
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D002460:Cell Line; D009033:Culicidae / Q000469:parasitology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D005786:Gene Expression Regulation; D018390:Gene Targeting; D008018:Life Cycle Stages; D008099:Liver / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010962:Plasmodium berghei / Q000166:cytology / Q000201:enzymology* / Q000472:pathogenicity / Q000648:ultrastructure; D014176:Protein Biosynthesis; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000469:parasitology* / Q000648:ultrastructure; D034101:Sporozoites / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D012333:RNA, Messenger; D019892:eIF-2 Kinase; D010749:Phosphoprotein Phosphatases