Abstract
BackgroundThe production of gametocytes is essential for transmission of malaria parasites from the mammalian host to the mosquito vector. However the process by which the asexual blood-stage parasite undergoes commitment to sexual development is not well understood. This process is known to be sensitive to environmental stimuli and it has been suggested that a G protein dependent system may mediate the switch, but there is little evidence that the Plasmodium falciparum genome encodes heterotrimeric G proteins. Previous studies have indicated that the malaria parasite can interact with endogenous erythrocyte G proteins, and other components of the cyclic nucleotide pathway have been identified in P. falciparum. Also, the polypeptide cholera toxin, which induces commitment to gametocytogenesis is known to catalyze the ADP-ribosylation of the αs class of heterotrimeric G protein α subunits in mammalian systems has been reported to detect a number of Gα subunits in P. falciparum-infected red cells.MethodsCholera toxin and Mas 7 (a structural analogue of Mastoparan) were used to assess the role played by putative G protein signalling in the commitment process, both are reported to interact with different components of classical Gαs and Gαi/o signalling pathways. Their ability to induce gametocyte production in the transgenic P. falciparum line Pfs16-GFP was determined and downstream effects on the secondary messenger cAMP measured.ResultsTreatment of parasite cultures with either cholera toxin or MAS 7 resulted in increased gametocyte production, but only treatment with MAS 7 resulted in a significant increase in cAMP levels. This indicates that MAS 7 acts either directly or indirectly on the P. falciparum adenylyl cyclase.ConclusionThe observation that cholera toxin treatment did not affect cAMP levels indicates that while addition of cholera toxin does increase gametocytogenesis the method by which it induces increased commitment is not immediately obvious, except that is unlikely to be via heterotrimeric G proteins.
Highlights
The production of gametocytes is essential for transmission of malaria parasites from the mammalian host to the mosquito vector
The number of gametocytes present at 0 hours was subtracted from the number of gametocytes present at 96 hours to obtain the total number of gametocytes produced during the 96-hour assay period
If acting canonically it catalyzes the ADP-ribosylation of the αs class of heterotrimeric G protein α subunits and it has been reported to detect a number of Gα subunits in P. falciparum-infected red cells [13]
Summary
The production of gametocytes is essential for transmission of malaria parasites from the mammalian host to the mosquito vector. The process by which the asexual blood-stage parasite undergoes commitment to sexual development is not well understood This process is known to be sensitive to environmental stimuli and it has been suggested that a G protein dependent system may mediate the switch, but there is little evidence that the Plasmodium falciparum genome encodes heterotrimeric G proteins. A switch from asexual to sexual development resulting in the production of gametocytes is essential for transmission of the malaria parasite to the mosquito vector but the mechanisms behind this switch are still poorly understood. While there is little evidence that the Plasmodium falciparum genome encodes heterotrimeric G proteins [9,10], previous studies have indicated that the malaria parasite can interact with endogenous erythrocyte G proteins [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
