Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development

Both cholera and pertussis toxins were used to label and study the expressi on of heterotrimeric G protein alpha subunits in Plasmodium falciparum extr acts. Expression of these proteins is developmentally regulated throughout the erythrocytic cycle with peak expression during early asexual developmen t and in mature sexual stages. Treatment of P. falciparum cultures with cho lera toxin causes an increase in conversion to sexual development, and at t he same concentration has a marginal inhibitory effect on asexual growth an d division. Through precise synchronisation of the parasites' asexual cell cycle, we have defined the period of sensitivity to this induction at aroun d the time of invasion, one cycle before the development of the sexual form . Fluorescent microscopy confirmed that access of the toxin to the parasite is limited to the invasive form - the free merozoite, while further labell ing studies revealed expression of a single G protein alpha subunit in thes e stages. These observations are consistent with the view that a G protein- dependent signal transduction pathway is involved in coupling the parasite' s environment to commitment to sexual development (gametocytogenesis). This means of artificially stimulating the pathways leading to sexual developme nt can now be used to biochemically follow the activation of the signalling pathways involved. (C) 2000 Elsevier Science B.V. All rights reserved.