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

TL;DR

The study explores how the ist-1 gene in C. elegans affects resistance to starvation during early development, both through and independent of a known signaling pathway.

Contribution

The study reveals that ist-1/IRS1 influences L1 starvation resistance via DAF-16/FoxO-dependent and -independent mechanisms.

Findings

ist-1/IRS1 mutants show increased larval growth and reproduction after L1 starvation.

ist-1/IRS1 promotes DAF-16 nuclear localization in starved larvae, suggesting involvement in insulin signaling.

ist-1/IRS1 also functions independently of DAF-16/FoxO, indicating novel roles.

Abstract

The mammalian IRS1 gene is an important adaptor for the insulin and insulin-like growth factor receptors, but its sole homolog in the nematode

C. elegans

,

ist-1

, has received relatively little attention. We show that

ist-1
/IRS1

has modest effects on L1 starvation resistance, with two null mutants increasing larval growth and reproduction after recovery from extended L1 arrest.

ist-1
/IRS1

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

ist-1
/IRS1

also functions independently of

daf-16
/FoxO

, suggesting additional, novel function.

Figures