In C. elegans,
daf-2 encodes the sole ortholog of the insulin /IGF-like receptor and 40 candidate insulin-like ligands have been described. We hypothesized that the existence of an insulin binding protein in the worm would provide an attractive mechanism for regulating the interaction of different insulin peptides with the receptor. To that end, we noted the existence of an alternatively spliced, truncated isoform of
daf-2, termed
daf-2b, that is predicted to encode the extracellular ligand binding domain but lack the transmembrane and intracellular signaling domains. Since this truncated isoform retains the potential to bind insulin peptides, but cannot transduce a signal, it could inhibit
daf-2 signaling by acting as a decoy receptor or soluble binding protein. Immunoprecipitation of FLAG tagged DAF-2B from transgenic worms indicated that the short isoform is able to form disulfide-linked dimers, which could allow it to bind insulin peptides with high affinity. Furthermore, we find that over-expression of the
daf-2b isoform confers phenotypes consistent with reduced insulin signaling, including increased dauer entry and reduced recovery, increased thermal stress resistance and
daf-16 dependent lifespan extension. Truncated isoforms of mammalian insulin receptors, similar to
daf-2b, could represent a novel, conserved regulatory mechanism within the insulin axis.