Characterization and functional deorphanization of CCHamides and their receptors in the yellow fever mosquito, Aedes aegypti

Studying the neuroendocrine system of mosquitoes, which transmit various pathogens leading to human diseases, allows us to better understand their physiology. Novel CCHamide neuropeptides, CCHa1 and CCHa2, and their associated receptors, CCHa1R and CCHa2R, were recently identified across insects, but they have not been studied in mosquitoes. This study aims to quantify and localize expression of CCHamides and CCHa2R to determine their physiological role in the mosquito, Aedes aegypti. Results revealed adults express the most CCHamide transcripts while CCHa2R transcript was enriched in pupa. The midgut was found to be the primary source for both CCHamide transcripts while higher CCHa2R transcript abundance was detected in the hindgut and the reproductive system. Both CCHamide receptors, the CCHa1R and CCHa2R, were deorphanized, revealing CCHamides exhibited the strongest ligand activity. CCHa2 and CCHa2R transcripts were unresponsive to either sucrose ingestion or starvation stress while CCHa1 and CCHa2 transcript levels responded to a blood-meal.