gametogenesis in malaria parasites is mediated by the cgmp-dependent protein kinase配子形成cgmp-dependent在疟疾寄生虫介导的蛋白激酶.pdfVIP
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gametogenesis in malaria parasites is mediated by the cgmp-dependent protein kinase配子形成cgmp-dependent在疟疾寄生虫介导的蛋白激酶
PLoS BIOLOGY
Gametogenesis in Malaria Parasites
Is Mediated by the cGMP-Dependent
Protein Kinase
1 1 1¤ 1 1 1
Louisa McRobert , Cathy J. Taylor , Wensheng Deng , Quinton L. Fivelman , Ross M. Cummings , Spencer D. Polley ,
2 1*
Oliver Billker , David A. Baker
1 Department of Infectious and Tropical Diseases, London School of Hygiene Tropical Medicine, London, United Kingdom, 2 Wellcome Trust Sanger Institute, Hinxton,
Cambridge, United Kingdom
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 (Ca2þ)
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.
Citation: McRobe
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