A decade with the juvenile hormone receptor

Juvenile hormone (JH) and ecdysteroids represent equally important nonpeptide signals governing insect reproduction and development. For a considerable time, understanding of JH action lagged behind ecdysteroid research. Arriving with a 20-year delay, the intracellular receptor for JH was finally identified as a ligand-activated bHLH-PAS transcription factor, originally named Methoprene-tolerant (Met), by virtue of the resistance Drosophila mutants exhibited to morphogenetic and lethal actions of JH and its mimic methoprene. Systemic RNAi in suitable insect models revealed the anticipated function of Met in preventing metamorphosis and promoting reproduction, thus providing the missing link to the chief roles of JH in insects. That, along with defining the JH-binding pocket and the JH-response DNA elements of Met, established the JH receptor (JHR) 10 years ago. After reviewing the functional attributes of the JHR, this chapter will focus on advances in the genetics, cell biology, and biochemistry of the JHR achieved during this past decade. Although hormone receptor function of bHLH-PAS transcription factors is unprecedented, the well-studied mammalian aryl hydrocarbon receptor (AhR) belonging to the same protein family affords functional parallels with the JHR. We can now begin to understand the mechanisms of JHR interaction with the chaperone Hsp90/83, nucleocytoplasmic transport and post-translational regulation by phosphorylation, dimerization with bHLH-PAS partner proteins, and activation by agonist ligands binding to the PAS-B domain. A section is dedicated to current efforts exploiting the JHR as a basis of chemical high-throughput screening, aimed at discovery of novel compounds for environmentally friendly control of insect pests and disease vectors.