mTOR Regulates Phase Separation of PGL Granules to Modulate Their Autophagic Degradation.

ABSTRACT

The assembly of phase-separated structures is thought to play an important role in development and disease, but little is known about the regulation and function of phase separation under physiological conditions. We showed that during C. elegans embryogenesis, PGL granules assemble via liquid-liquid phase separation (LLPS), and their size and biophysical properties determine their susceptibility to autophagic degradation. The receptor SEPA-1 promotes LLPS of PGL-1/-3, while the scaffold protein EPG-2 controls the size of PGL-1/-3 compartments and converts them into less dynamic gel-like structures. Under heat-stress conditions, mTORC1-mediated phosphorylation of PGL-1/-3 is elevated and PGL-1/-3 undergo accelerated phase separation, forming PGL granules that are resistant to autophagic degradation. Significantly, accumulation of PGL granules is an adaptive response to maintain embryonic viability during heat stress. We revealed 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.