Imaginal discs produce neuropeptide-like precursor 1 to alleviate ER stress in response to warm temperatures

In mammals, prolonged heat stress induces an endoplasmic reticulum (ER) stress response that can damage internal organs. In Drosophila, larvae grow and develop into adults faster at warmer temperatures (e.g., 30°C) than at lower temperatures, but with reduced body size and fertility. In this study, we show that the neuropeptide gene neuropeptide-like precursor 1 (Nplp1) alleviates temperature-induced ER stress in imaginal discs. Warm temperatures increase production of a specific Nplp1 splice variant that inhibits PKR-like endoplasmic reticulum kinase (PERK) activation and cell death. Nplp1 inhibits Dilp8 expression through the PERK/ATF4/Yki pathway, thereby enabling imaginal disc growth and ecdysone homeostasis under warm temperature conditions. These findings provide valuable insights into how animals cope with elevated temperatures. The insect neuropeptide Nplp1 suppresses endoplasmic reticulum stress, thereby safeguarding the homeostasis of organs and the endocrine system in developing organisms under stressful, high-temperature conditions.