Location: Chemistry ResearchTitle: Sesquiterpene action, and morphogenetic signaling through the ortholog of retinoid X receptor, in higher Diptera) Author
Submitted to: General and Comparative Endocrinology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/11/2013
Publication Date: 12/1/2013
Citation: Jones, D., Jones, G., Teal, P.E. 2013. Sesquiterpene action, and morphogenetic signaling through the ortholog of retinoid X receptor, in higher Diptera. General and Comparative Endocrinology. 194:326-335. Interpretive Summary: Insect Juvenile Hormone has long been held to be the only sesquiterpene hormone affecting insect growth and development. There are a number of physiological processes that have been attributed, for lack of an alternative, to JH (and more recently its receptor MET), but for which the JH/MET axis has not provided a satisfactory mechanistic explanation. However, scientists at the Center for Medical Agricultural and Veterinary Entomology, USDA-ARS, Gainesville Florida, in collaboration with scientists at the Graduate Center for Toxicology and Department of Biology, University of Kentucky, Lexington Kentucky recently identified methyl farnesoate as a circulating hormone in Fruit flies. They demonstrated that levels of endogenous methyl farnesoate are both sufficient and necessary to load the receptor and thus regulate metamorphosis from the larva to the adult form. In establishing a methyl farnesoate/RXR endocrine axis that is distinct from JH/MET protein, the studies offer a long sought solution to issues that have bedeviled the field of insect endocrinology. The new insect endocrine axis established here of methyl farnesoate/RXR offers a solution to at least some of unresolved mechanistic questions in insect endocrinology.
Technical Abstract: Morphogenetic signaling by small terpenoid hormones is a common feature of both vertebrate and invertebrate development. Most attention on insect developmental signaling by small terpenoids has focused on signaling by juvenile hormone through bHLH-PAS proteins (e.g., the MET protein), especially as that signaling axis intersects with ecdysteroid action through the receptor EcR. However, a series of endocrine and pharmacological studies on pupariation in cyclorrhaphous Diptera have remained persistently refractory to explanation with the above two-axis model. Recently, the terpenoid compound methyl farnesoate has been physicochemically demonstrated to exist in circulation at physiological concentrations, in several mecopterid orders, including Diptera. In addition, it has also been recently demonstrated that the receptor to which methyl farnesoate binds with nanomolar affinity (ultraspiracle, an ortholog of retinoid X receptor) requires a functioning ligand binding pocket to sustain the morphogenetic transition to puparium formation. This review evaluates endocrine and pharmacological evidence for developmental pathways reached by methyl farnesoate action, and assesses the participation of the retinoid X receptor ligand pocket in signal transduction to those developmental endpoints.