The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands

Min Zhang, Clare Fennell, Lisa Ranford-Cartwright, Ramanavelan Sakthivel, Pascale Gueirard, Stephan Meister, Anat Caspi, Christian Doerig, Ruth S. Nussenzweig, Renu Tuteja, William Sullivan, David S. Roos, Beatriz M A Fontoura, Robert Ménard, Elizabeth A. Winzeler, Victor Nussenzweig

Research output: Contribution to journalArticle

78 Citations (Scopus)

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-2α (eIF2α) 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 eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α 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.

Original languageEnglish
Pages (from-to)1465-1474
Number of pages10
JournalJournal of Experimental Medicine
Volume207
Issue number7
DOIs
StatePublished - Jul 5 2010

Fingerprint

Eukaryotic Initiation Factor-2
Sporozoites
Plasmodium
Salivary Glands
Culicidae
Phosphotransferases
Phosphoric Monoester Hydrolases
Parasites
Liver
Eukaryotic Cells
Life Cycle Stages
Malaria
Insects
Hepatocytes
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Zhang, M., Fennell, C., Ranford-Cartwright, L., Sakthivel, R., Gueirard, P., Meister, S., ... Nussenzweig, V. (2010). The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. Journal of Experimental Medicine, 207(7), 1465-1474. https://doi.org/10.1084/jem.20091975

The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. / Zhang, Min; Fennell, Clare; Ranford-Cartwright, Lisa; Sakthivel, Ramanavelan; Gueirard, Pascale; Meister, Stephan; Caspi, Anat; Doerig, Christian; Nussenzweig, Ruth S.; Tuteja, Renu; Sullivan, William; Roos, David S.; Fontoura, Beatriz M A; Ménard, Robert; Winzeler, Elizabeth A.; Nussenzweig, Victor.

In: Journal of Experimental Medicine, Vol. 207, No. 7, 05.07.2010, p. 1465-1474.

Research output: Contribution to journalArticle

Zhang, M, Fennell, C, Ranford-Cartwright, L, Sakthivel, R, Gueirard, P, Meister, S, Caspi, A, Doerig, C, Nussenzweig, RS, Tuteja, R, Sullivan, W, Roos, DS, Fontoura, BMA, Ménard, R, Winzeler, EA & Nussenzweig, V 2010, 'The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands', Journal of Experimental Medicine, vol. 207, no. 7, pp. 1465-1474. https://doi.org/10.1084/jem.20091975
Zhang, Min ; Fennell, Clare ; Ranford-Cartwright, Lisa ; Sakthivel, Ramanavelan ; Gueirard, Pascale ; Meister, Stephan ; Caspi, Anat ; Doerig, Christian ; Nussenzweig, Ruth S. ; Tuteja, Renu ; Sullivan, William ; Roos, David S. ; Fontoura, Beatriz M A ; Ménard, Robert ; Winzeler, Elizabeth A. ; Nussenzweig, Victor. / The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 7. pp. 1465-1474.
@article{66b429bc54a5480888df1830233e2e0b,
title = "The Plasmodium eukaryotic initiation factor-2α 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-2α (eIF2α) 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 eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α 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.",
author = "Min Zhang and Clare Fennell and Lisa Ranford-Cartwright and Ramanavelan Sakthivel and Pascale Gueirard and Stephan Meister and Anat Caspi and Christian Doerig and Nussenzweig, {Ruth S.} and Renu Tuteja and William Sullivan and Roos, {David S.} and Fontoura, {Beatriz M A} and Robert M{\'e}nard and Winzeler, {Elizabeth A.} and Victor Nussenzweig",
year = "2010",
month = "7",
day = "5",
doi = "10.1084/jem.20091975",
language = "English",
volume = "207",
pages = "1465--1474",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands

AU - Zhang, Min

AU - Fennell, Clare

AU - Ranford-Cartwright, Lisa

AU - Sakthivel, Ramanavelan

AU - Gueirard, Pascale

AU - Meister, Stephan

AU - Caspi, Anat

AU - Doerig, Christian

AU - Nussenzweig, Ruth S.

AU - Tuteja, Renu

AU - Sullivan, William

AU - Roos, David S.

AU - Fontoura, Beatriz M A

AU - Ménard, Robert

AU - Winzeler, Elizabeth A.

AU - Nussenzweig, Victor

PY - 2010/7/5

Y1 - 2010/7/5

N2 - 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-2α (eIF2α) 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 eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α 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.

AB - 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-2α (eIF2α) 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 eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α 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.

UR - http://www.scopus.com/inward/record.url?scp=77954394670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954394670&partnerID=8YFLogxK

U2 - 10.1084/jem.20091975

DO - 10.1084/jem.20091975

M3 - Article

C2 - 20584882

AN - SCOPUS:77954394670

VL - 207

SP - 1465

EP - 1474

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

ER -