报告题目：mTOR signaling controls phase separation of PGL granules to orchestrate their autophagic degradation and heat stress adaptation during C. elegans development
报告时间：7月31日，星期二，10:00 ~ 11:00
摘要：The assembly of structures by phase separation is thought to play an important role in normal development and disease, but little is known about the regulation and function of this process under physiological conditions. Here we showed that during C. elegans embryogenesis, the biophysical properties of PGL granules assembled via liquid-liquid phase separation (LLPS) determine their autophagic degradation and stress-resistance function. The receptor protein SEPA-1 and the scaffold protein EPG-2 modulate LLPS of PGL granules to specify their autophagic degradation. SEPA-1 promotes LLPS of PGL-1/-3, while EPG-2 controls the size of PGL compartments and also converts them into less dynamic gel-like structures. mTORC1 directly phosphorylates PGL-1/-3 to facilitate LLPS, and thus plays dual roles in regulating PGL granule degradation. Under normal growth conditions, mTORC1 promotes condensation of diffuse PGL-1/-3 into granules for efficient removal of diffuse PGL proteins. Under heat stress conditions, mTORC1-mediated phosphorylation of PGL-1/-3 is elevated and their phase separation is greatly enhanced, making them refractory to autophagic degradation. Significantly, formation of PGL granules is an adaptive response to maintain embryonic viability during heat stress. Our study reveals that mTORC1-mediated LLPS of PGL-1/-3 acts as a switch-like stress sensor, coupling phase separation to autophagic degradation and adaptation to stress during development.