Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase

@article{citeulike:2859910, 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\&\#43;) 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.}, author = {Mcrobert, Louisa and Taylor, Cathy J. and Deng, Wensheng and Fivelman, Quinton L. and Cummings, Ross M. and Polley, Spencer D. and Billker, Oliver and Baker, David A.}, citeulike-article-id = {2859910}, doi = {10.1371/journal.pbio.0060139}, journal = {PLoS Biology}, keywords = {gametes}, month = {June}, number = {6}, pages = {e139+}, posted-at = {2008-06-07 10:10:30}, priority = {2}, title = {Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase}, url = {http://dx.doi.org/10.1371/journal.pbio.0060139}, volume = {6}, year = {2008} }

TY - JOUR ID - citeulike:2859910 L3 - citeulike-article-id:2859910 N2 - 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. IS - 6 JF - PLoS Biology TI - Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase VL - 6 SP - e139 KW - gametes AU - Mcrobert, Louisa AU - Taylor, Cathy AU - Deng, Wensheng AU - Fivelman, Quinton AU - Cummings, Ross AU - Polley, Spencer AU - Billker, Oliver AU - Baker, David PY - 2008/06/01/ UR - http://dx.doi.org/10.1371/journal.pbio.0060139 ER -