A seven-helix protein acts as a key regulator of translation during human-to-mosquito transmission of Plasmodium falciparum. Plasmodium falciparum

Plasmodium falciparum is a unicellular parasite responsible for the majority of 440,000 death due to malaria every year. Due to their essential role for malaria transmission, gametocytes represent prime targets for transmission-blocking strategies intended to prevent spread of the deadly disease. In this study, we explored the signaling pathways leading to gametogenesis and identified a hitherto unknown protein, which structurally belongs to the class of seven-helix proteins and which thus was termed 7-helix-1. The protein is specifically expressed in female gametocytes and gene disruption leads to impaired gamete formation and thus reduced transmission of malaria parasites to mosquitoes. The loss of 7-helix-1 caused significant changes in the expression of components of the molecular machinery needed by eukaryotic cells to synthesize proteins. We thus propose that 7-helix-1 is a key regulator needed to coordinate the increased need of proteins at the onset of gametogenesis. Overall design: Plasmodium falciparum parasite strains WT NF54 and 7-Helix-1-KO 2E6 were Percoll-enriched for mature (stage V) gametocytes were activated with 100 µM Xanthurenic acid for 30 minutes at RT. Total RNA was isolated using the Trizol reagent (Invitrogen) according to the manufacturer’s protocol. The extracted RNA was then hybridized on a DNA microarray against a common reference pool.