Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling via the intestinal peptide transporter PEPT-1

Abstract

AbstractGametogenesis involves active protein synthesis and heavily relies on proteostasis. How animals regulate germline proteostasis at the organismal level is poorly understood. TakingC. elegansas a model, we show that germline proteostasis requires coupled activities of HSF-1-dependent protein folding and insulin/IGF-1 signaling controlled protein synthesis. Depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, declines in fecundity and gamete quality. Reduced insulin/IGF-1 signaling confers germ cells’ resilience to limited protein folding capacity and proteotoxic stress by lowering ribosome biogenesis and the rate of translation. Interestingly, insulin/IGF-1 signaling promotes the expression of the evolutionarily conserved intestinal peptide transporter PEPT-1 via its downstream transcription factor FOXO/DAF-16, therefore allowing dietary proteins to be incorporated into an amino acid pool that fuels protein synthesis in the germline. We propose that this non-cell-autonomous pathway plays a critical role in regulating proteostasis in gametogenesis.TeaserInsulin/IGF-1 signaling regulates proteostasis in gametogenesis via the control of dietary protein absorption.