Draper‐ATG3 Interaction Positively Regulates Autophagy to Mediate Silk Gland Degradation in Bombyx mori

Autophagy critically regulates developmental cell death during insect metamorphosis, yet the regulatory mechanisms underlying autophagy-dependent cell death remain poorly defined. Here, the engulfment receptor Draper's essential role in tissue clearance and remodeling is reported. Initially, it is shown that Draper is evolutionarily conserved in most insect species. CRISPR/Cas9-mediated knockout in the lepidopteran model Bombyx mori demonstrates that Draper deficiency impairs autophagy activation and delays middle silk gland degradation during metamorphosis, while its overexpression enhances autophagy induction. Proteomic profiling reveals that loss of Draper disrupts silk protein metabolism, ubiquitin signaling, and autophagic substrate degradation. Through liquid chromatography-tandem mass spectrometry and coimmunoprecipitation, a direct Draper-autophagy-related protein 3 (ATG3) interaction is identified, which enhances autophagic activity. These findings bridge a critical knowledge gap in how developmental signals mechanistically engage core autophagy machinery to ensure precise tissue remodeling. This study redefines autophagy initiation paradigms by identifying Draper as an evolutionarily conserved regulator, providing a unified framework integrating developmental timing, phagocyte signaling, and metabolic clearance in metamorphosis.