Insect juvenile hormone receptor Methoprene-tolerant (Met)

The Insect juvenile hormone receptor Methoprene-tolerant (Met) is a member of the basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family of transcription factors (Jindra et al., 2013, Annual Review of Entomology). It functions as the primary intracellular receptor for juvenile hormone (JH), a sesquiterpenoid that is vital for controlling insect development, molting, and reproductive maturation (Charles et al., 2011, PNAS). When JH binds to the PAS-B domain of Met, it triggers the formation of a heterodimer with the co-activator protein Taiman (Tai). This complex then binds to juvenile hormone response elements (JHREs) to activate the transcription of genes such as Krüppel homolog 1 (Kr-h1), which maintains the insect in its current larval or nymphal stage (Kayukawa et al., 2012, PNAS). Met is a significant target for biorational insecticides known as juvenile hormone analogs (JHAs), including methoprene and pyriproxyfen, which are used to control agricultural pests and disease vectors like mosquitoes (Dhadialla et al., 1998, Annual Review of Entomology). These compounds act as agonists that mimic the natural hormone, leading to developmental disruption, failure to reach adulthood, or sterility (Wilson, 2004, Annual Review of Entomology). Because JH signaling is absent in vertebrates, drugs targeting Met generally exhibit high safety profiles for humans and other mammals. However, therapeutic challenges include the development of metabolic and target-site resistance in insect populations and potential toxicity to non-target aquatic arthropods (Cornel et al., 2002, Journal of Medical Entomology).

Other names

Methoprene-tolerant proteinJuvenile hormone receptorMetbHLH-PAS transcription factor Met

Agonist binding to the PAS-B domain, inducing heterodimerization with Taiman and subsequent transcriptional activation of juvenile hormone-responsive genes.