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Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase

McRobert, Louisa, Taylor, Cathy J., Deng, Wensheng, Fivelman, Quinton L., Cummings, Ross M., Polley, Spencer D., Billker, Oliver and Baker, David A. 2008. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase. PLoS Biology 6 (6) , e139. 10.1371/journal.pbio.0060139

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Abstract

Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA), can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP) stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG) inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+) is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR355 Virology
Publisher: Public Library of Science
ISSN: 1544-9173
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:17
URI: http://orca-mwe.cf.ac.uk/id/eprint/45666

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