The Plasmodium eukaryotic initiation factor-2alpha kinase IK2 controls the latency of sporozoites in the mosquito salivary glands.
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.
Zhang
Min
M
Michael Heidelberger Division, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Fennell
Clare
C
Ranford-Cartwright
Lisa
L
Sakthivel
Ramanavelan
R
Gueirard
Pascale
P
Meister
Stephan
S
Caspi
Anat
A
Doerig
Christian
C
Nussenzweig
Ruth S
RS
Tuteja
Renu
R
Sullivan
William J
WJ
Roos
David S
DS
Fontoura
Beatriz M A
BM
Ménard
Robert
R
Winzeler
Elizabeth A
EA
Nussenzweig
Victor
V
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*
D015800:Protozoan Proteins; D012333:RNA, Messenger; D019892:eIF-2 Kinase; D010749:Phosphoprotein Phosphatases