The role of Anopheles gambiae vitellogenin in nutrient transport, fertility and Plasmodium falciparum development

Abstract

The female Anopheles gambiae mosquito, which is the main vector of the human malaria parasite Plasmodium falciparum, feeds on blood to develop eggs. After ingesting a bloodmeal, she produces a yolk precursor protein called vitellogenin (Vg) and deposits it into the oocyte for amino acid needs of the embryo. This dissertation shows that vitellogenin is essential to An. gambiae reproduction, as its depletion results in complete infertility. Vg silencing causes major dysregulation of amino acid and protein deposition in eggs, leading to upregulation of TOR signaling. In turn, such upregulation leads to enhanced transcription of the lipid transporter lipophorin (Lp), inducing excessive triglyceride deposition into the ovaries. Embryonic lethality occurs early during development and is likely caused by severe amino acid deprivation. Vg depletion in infected females also leads to accelerated rates of P. falciparum development, most likely mediated by both increased amino acid levels and Lp-transported lipids, so that mosquitoes become infectious to humans in a shorter period of time. Combined, this work reveals previously unknown dynamics between two major mosquito nutrient transporters, and shows that although Vg is an attractive target to induce sterility in field populations, preventing its expression would potentially lead to more effective transmission of malaria parasites.