Volume 9 Supplement 1

4th International Conference of cGMP Generators, Effectors and Therapeutic Implications

Open Access

The role of the cGMP-dependent protein kinase in development of the malaria parasite

  • Louisa McRobert1,
  • Helen M Taylor2,
  • Cathy J Taylor1,
  • Wensheng Deng1,
  • Robert W Moon3, 4,
  • Quinton L Fivelman1,
  • Munira Grainger3,
  • Spencer D Polley1,
  • Audrey Sicard2,
  • Oliver Billker4,
  • Anthony A Holder3 and
  • David A Baker1Email author
BMC Pharmacology20099(Suppl 1):S2

https://doi.org/10.1186/1471-2210-9-S1-S2

Published: 11 August 2009

The life cycle of the malaria parasite Plasmodium is complex with distinct phases occurring in the human host and the mosquito vector. Proliferation of asexual parasites within blood cells leads to pathology whereas a distinct sexual stage is required to mediate transmission to the insect. There is a surprising lack of information about how progression of the life cycle is controlled. By analogy with other systems, it is likely that differentiation is regulated by intracellular signalling cascades involving specific phosphorylation/dephosphorylation events. Following an early report in the literature suggesting a role for the parasite cGMP signalling pathway in male gametogenesis, our recent work has investigated the role of the P. falciparum cGMP-dependent protein kinase (PfPKG) in the parasite life cycle. We have used specific inhibitors of the parasite PKG in conjunction with transgenic parasites expressing an inhibitor-insensitive PfPKG to provide direct evidence of a role for this kinase in gametogenesis [1]. Furthermore, we have used this approach recently to elucidate a central role for PfPKG in the late events of P. falciparum asexual blood stage schizogony. Using the P. berghei mouse malaria model we have also demonstrated a role for the kinase in gliding motility of the ookinete; the zygote form that borrows through the insect midgut wall. Discovery of essential functions for PfPKG in multiple developmental stages suggest that it may be a good target for new anti-malarial drugs.

Authors’ Affiliations

(1)
London School of Hygiene & Tropical Medicine
(2)
Wellcome Centre for Molecular Parasitology, University of Glasgow
(3)
Medical Research Council National Institute for Medical Research
(4)
Wellcome Trust Sanger Institute

References

  1. McRobert , Taylor CJ, Deng W, Fivelman QL, Cummings RM, Polley SD, Billker O, Baker DA: Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase. PLoS Biol. 2008, 6: e139-10.1371/journal.pbio.0060139.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© McRobert et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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