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

Zhang, M. et al. (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), pp. 1465-1474. (doi: 10.1084/jem.20091975)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fennell, Miss Clare and Doerig, Dr Christian and Ranford-Cartwright, Dr Lisa
• Authors: Zhang, M., Fennell, C., Ranford-Cartwright, L., Sakthivel, R., Gueirard, P., Meister, S., Caspi, A., Doerig, C., Nussenzweig, R. S., Tuteja, R., Sullivan, W. J., Roos, D. S., Fontoura, B. M. A., Menard, R., Winzeler, E. A., and Nussenzweig, V.
• Subjects: Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Experimental Medicine
• Publisher: Rockefeller University Press
• ISSN: 0022-1007
• ISSN (Online): 1540-9538
• Published Online: 28 June 2010
• Copyright Holders: Copyright © 2010 The Authors
• First Published: First published in Journal of Experimental Medicine 207(7):1465
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher