Insect nuclear receptors

The insect nuclear receptors EcR and USP are main targets for the agrochemical research. The structures of their ligand-binding domain is an essential step in the development of new types of environmentally safe insecticides. For EcR, a new pharmacophore... 

Both nuclear receptors EcR and USP that form the functional receptor for ecdysone seem to have evolved in a concerted way during insect evolution. The evolutionary conserved divergences in the protein sequences of arthropod USPs-RXRs and EcRs are... 

The cDNAs for the glucocorticoid and the oestrogen receptors were isolated more than 15 years ago. They were among the first genes, coding for transcriptional gene activators, to be identified. The family of nuclear receptors is the largest family of transcription factors. Until now, more than 150 different members of the superfamily of nuclear receptors, from worms to insects to humans, have been described. The discovery of an insect receptor for a steroid hormone, ecdysone, indicated that this kind of receptor must have evolved prior to the separation of vertebrates and invertebrates. 

Nuclear receptors for the steroid hormone ecdysone in Drosophila deserve special consideration, for several reasons. First, the insect hormone ecdysone (Fig. 11.2) was the first steroid hormone shown to act at the level of the gene, because it induced puffs in the giant chromosomes of the fruitfly. Secondly, ecdysone activates the developmental programme of Drosophila, and, finally, the sequences of the DNA-binding domain (DBD) of the Drosophila nuclear ecdysone receptor and of receptor homologues (for example, the COUP-TFs chicken ovalbumin upstream promoter transcription factors) are highly conserved and nearly identical in vertebrates and humans. 

Like vertebrate steroid hormones, ecdysteroids recognize target tissues by binding with nuclear receptors. The ecdysteroid receptor has been isolated and characterized from the fiddler crab, Uca pugilator. It has been sequenced and has homologies with insect ecdysteroid receptors. Transcripts for the receptor were isolated from crab limb buds and developing ovaries. 

Although ecdysone is the only steroid hormone in Drosophila of which the function is known, the haemolymph of the fly contains many other ecdysteroids, the function of which remains to be clarified. The haemolymph also contains the sesquiterpenoid, juvenile hormone (JH). In many insects, JH r ulates ecdysone release. JH has structural features in common with the retinoids and may signal through a nuclear RXR receptor. 

---