Search

International audience; The ecdysteroids (Ec), invertebrate steroid hormones, elicit genomic but also non-genomic effects. By analogy to vertebrates, non-genomic responses towards Ec may be mediated not only by distinct membrane-integrated but also by membrane-associated receptors like the classical nuclear ecdysteroid receptor (EcR) of arthropods. This is supported by a comparison of physiological properties between invertebrate and vertebrate steroid hormone systems and recent findings on the subcellular localization of EcR. The measured or predicted high degree of conformational flexibility of both Ec and the ligand binding domain (LBD) of EcR give rise to a conformational compatibility model: the compatibility between conformations of the cognate receptor's ligand binding domain and structures or conformations of the ligand would determine their interaction and eventually the initiation of genomic versus non-genomic pathways. This model could also explain why specific non-genomic effects are generally not observed with non-steroidal agonists of the bisacylhydrazine group.

International audience; This chapter summarizes the present knowledge on the ecdysteroid receptor (EcR) structure and function with special emphasis on those aspects that are relevant for gene switch applications, and describes gene switch technology with a focus on EcR‐based gene switches. The EcR is a member of the nuclear receptor superfamily and exhibits the typical modular structure composed of the N‐terminal A/B domain, the DNA‐binding C domain, the hinge (D) region, the ligand‐binding E domain, and the C-terminal F domain. The ligand‐binding domain is multifunctional and includes ligand‐dependent dimerization and transactivation functions, while ligand‐independent transactivation and dimerization functions are found in the terminal domains and in the region spanning the DNA binding domain and the N‐terminal region of the hinge, respectively. The EcR heterodimerizes with other members of the nuclear receptor superfamily noticeably with the ultraspiracle protein (USP), which is an orthologue of the vertebrate retinoic acid X receptor (RXR). The progress in made in EcR research has shown that the ligand‐binding pocket of EcR is highly flexible and adaptable. This property of EcR permits the development of receptor systems for practical application in medicine and agriculture. The application of EcR‐based gene switch technology in cellular systems toward functional genomics, drug and ligand discovery, and therapeutic protein production has already commenced grow rapidly in near future. The application of EcR‐based gene switches in plants has a great potential and benefits greatly from the fact that several potential ligands represent registered insecticides and have a track record of environmental safety.