ist-1/IRS1 affects L1 starvation resistance in daf-16/FoxO-dependent and independent fashion

The mammalian IRS1 gene is an important adaptor for the insulin and insulin-like growth factor receptors, but its sole homolog in the nematode <i>C. elegans</i> , <i>ist-1</i> , has received relatively little attention. We show that <i>ist-1 /IRS1</i> has modest effects on L1 starvation resistance, with two null mutants increasing larval growth and reproduction after recovery from extended L1 arrest. <i>ist-1 /IRS1</i> mutants increase nuclear localization of DAF-16 /FoxO, a critical effector of insulin/IGF signaling, in starved L1 larvae, consistent with IST-1 /IRS1 transducing DAF-2 /IGFR signaling. However, epistasis analysis suggests that <i>ist-1 /IRS1</i> also functions independently of <i>daf-16 /FoxO</i> , suggesting additional, novel function.