Truncated insulin receptor isoform DAF-2B tunes insulin signalling via homodimer–heterodimer balance in C. elegans

Researchers at institutions including the laboratory of Matthew S. Gill have published a PLOS Genetics study examining how DAF-2B — a truncated, non-signalling, secreted isoform of the C. elegans insulin receptor DAF-2 — modulates insulin and insulin-like growth factor signalling (IIS) in the nematode.

DAF-2B lacks the intracellular kinase domain of the full-length receptor and has been characterised as a decoy receptor that sequesters insulin-like peptides (ILPs), which in C. elegans can act either as agonists or antagonists of DAF-2 signalling. The current study used a forward genetic screen for modifiers of DAF-2B protein expression, identifying a mutation in unc-31 — a gene encoding a calcium-dependent activator protein involved in neuropeptide secretion — that increased DAF-2B expression levels.

The authors go on to show that DAF-2B can form both homodimers and heterodimers with full-length DAF-2, and that the balance between these two species influences the overall output of the IIS pathway. Because IIS in C. elegans is a well-established model for conserved pathways governing metabolism, stress resistance, and longevity, the findings add mechanistic detail to how decoy receptor isoforms can tune signalling at the level of receptor complex composition rather than simply by ligand titration.

The study is published in PLOS Genetics and has completed peer review.