AHR38, a homolog of NGFI-B, inhibits formation of the functional ecdysteroid receptor in the mosquito Aedes aegypti

In anautogenous mosquitoes, vitellogenesis, the key event in egg maturation , requires a blood meal. Consequently, mosquitoes are vectors of numerous d evastating human diseases. After ingestion of blood, 20-hydroxyecdysone act ivates yolk protein precursor (YPP) genes in the metabolic tissue, the fat body. An important adaptation for anautogenicity is the previtellogenic dev elopmental arrest (the state-of-arrest) preventing the activation of YPP ge nes in previtellogenic females prior to blood feeding. Here, we show that a retinoid X receptor homolog, Ultraspiracle (AaUSP), which is an obligatory partner in the functional ecdysteroid receptor, exists at the state-of-arr est as a heterodimer with the orphan nuclear receptor AHR38, a homolog of D rosophila DHR38 and nerve growth factor-induced protein B, Yeast two-hybrid and glutathione S-transferase pull-down assays demonstrate that AHR38 can interact strongly with AaUSP, AHR38 also disrupts binding of ecdysteroid re ceptor to ecdysone response elements. Cell co-transfection of AHR38 with Aa EcR and AaUSP inhibits ecdysone-dependent activation of a reporter gene by the ecdysteroid receptor. Co-immunoprecipitation experiments indicate that AaUSP protein associates with AHR38 instead of AaEcR in fat body nuclei at the state-of-arrest.