Gonadotropin-releasing hormone-like receptor 2 inversely regulates somatic proteostasis and reproduction in Caenorhabditis elegans

The quality control machinery regulates the cellular proteome to ensure proper protein homeostasis (proteostasis). In Caenorhabditis elegans , quality control networks are downregulated cell-nonautonomously by the gonadal longevity pathway or metabolic signaling at the onset of reproduction. However, how signals are mediated between the gonad and the somatic tissues is not known. Gonadotropin-releasing hormone (GnRH)-like signaling functions in the interplay between development and reproduction and have conserved roles in regulating reproduction, metabolism, and stress. We, therefore, asked whether GnRH-like signaling is involved in proteostasis collapse at the onset of reproduction. Here, we examine whether C. elegans orthologues of GnRH receptors modulate heat shock survival. We find that gnrr-2 is required for proteostasis remodeling in different somatic tissues during the transition to adulthood. We show that gnrr- 2 likely functions in neurons downstream of the gonad in the gonadal-longevity pathway and modulate the somatic regulation of transcription factors HSF-1, DAF-16, and PQM-1. In parallel, gnrr-2 modulates egg-laying rates, vitellogenin production, and thus reproductive capacity. Taken together, our data suggest that gnrr-2 plays a GnRH-associated role, mediating the cross-talk between the reproduction system and the soma in the decision to commit to reproduction.