Insulin receptor substrate family member IST-1 regulates the development of Caenorhabditis elegans age-1 and aap-1 mutants

TL;DR

The study shows that the IST-1 protein in C. elegans plays a key role in regulating development through the insulin signaling pathway.

Contribution

The paper identifies IST-1 as a positive regulator of PI3K in C. elegans insulin signaling during development.

Findings

IST-1 mutants combined with age-1 and aap-1 mutations cause sterility and larval arrest in C. elegans.

IST-1 functions as a positive regulator of PI3K in the canonical insulin pathway.

No major interactions are observed with other genes in the insulin pathway.

Abstract

Insulin receptor substrate (IRS) is a class of adaptor proteins that mediate the activation of transmembrane tyrosine kinase receptors to downstream effectors. The
IST-1
protein is the sole IRS present in

Caenorhabditis elegans
,

which has been poorly studied in this animal model. Here, we show that

ist-1

mutants develop normally but exhibit sterility, larval arrest and dauer phenotypes when combined with mutations in

age-1

and

aap-1

genes, which encode the catalytic and regulatory subunits of phosphatidylinositol 3-kinase (PI3K), respectively. In contrast, no major genetic interactions are observed with mutations in other genes of the worm insulin pathway, either upstream or downstream
AGE-1
/
AAP-1
. We conclude that
IST-1
, the only IRS in

C. elegans

, functions as a positive regulator of PI3K in the canonical insulin pathway during development.

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