A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues.

Knockdown of the neuronal GPCR gene gtr-1 enhances protein degradation and modulates neuropeptide gene expression to influence proteostasis in C. elegans.

• Why it matters: Understanding how intertissue communication regulates proteostasis is crucial for addressing age-related neurodegenerative diseases, yet the mechanisms remain unclear.
• What they did: Researchers used gtr-1 knockdown in worms expressing different proteotoxic proteins to analyze changes in gene expression, protein aggregation, and degradation, revealing differential effects on neuropeptides and proteostasis.
• The result: Findings suggest neuropeptides act as organismal coordinators of proteostasis, and gtr-1 knockdown may mitigate proteotoxicity by enhancing protein degradation and altering neuropeptide signaling.