Erythropoiesis and molecular mechanisms for sexual determination in malaria parasites

Malaria parasites proliferate asexually within the vertebrate host but must undergo sexual reproduction for transmission to mosquitoes and hence infec tion of new hosts. The developmental pathways controlling gametocytogenesis are not known, but several protein kinases and other putative signal trans duction elements possibly involved in this phenomenon have been found in Pl asmodium. Recently, another developmental pathway, that of Plasmodium sex d etermination (male or female), has been shown to be triggered by erythropoi esis in the host. Rapid progress is being made in our understanding of the molecular basis of mammalian erythropoiesis, revealing kinase pathways that are essential to cellular responses triggered by the hormone erythropoieti n. Although the molecular mechanisms whereby this hormone modulates the sex ratio of malaria parasites remain to be elucidated, it probably activates, within the parasite, transduction pathways similar to those found in other eukaryotes, Indeed, enzymes belonging to protein kinase families known to be involved in the response of mammalian cells to erythropoietin (such as t he mitogen-activated protein kinases) have been identified in P. falciparum gametocytes. Some of these enzymes differ markedly from their mammalian ho mologs; therefore, identification of the transduction pathways of the paras ite that are responsible for its developmental response to erythropoietin o pens the way to the development of transmission-blocking drugs based on kin ase inhibitors.