Anopheles Cryptochrome 1: A novel regulator of malaria parasite transmission

Malaria kills about half a million people annually and has a tremendous socioeconomic impact. The disease is caused by Plasmodium parasites that are transmitted between humans by Anopheles mosquitoes. The lack of effective vaccines, and the parasite’s and mosquito’s resistance to drugs and insecticides, respectively, renders the control of malaria difficult, and novel control strategies are urgently needed. A better understanding of Anopheles-Plasmodium interactions can provide new malaria transmission-blocking targets. We have identified an intriguing Plasmodium antagonist function of the circadian photoreceptor Cryptochrome 1 (CRY1). CRY1 is enriched on the surface of P. falciparum-infected midguts, and its silencing renders the mosquito more permissive to parasite infection. Expression of key anti-Plasmodium immune genes did not change upon CRY1-silencing, suggesting that CRY1’s parasite-blocking does not involve the regulation of these known immune genes and mechanisms. We also showed that CRY1 silencing did not alter the total microbial load of the midgut, and is therefore unlikely to have an antibacterial role. CRY1 plays a photoreceptor in the circadian clock, but accumulating evidence also indicate light-independent functions. Cryptochrome chemical ligands result in significant reduction of the oocyst loads in the midguts, potentially due to their ability to stabilize CRY1. These data, taken together, suggest that CRY1 is likely to act against P. falciparum through a novel mechanism that warrants a better understanding.