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Phase separation and transition control autophagic degradation of PGL granules

Author: Update time: 2018-08-31

On August 30th, 2018, Dr. ZHANG Hong’s lab published a research article entitled “mTOR regulates phase separation of PGL granules to modulate their autophagic degradation” in Cell. This study found that mTORC1-mediated LLPS of PGL-1/-3 functions as a switch-like stress sensor, controlling phase separation of PGL-1/-3 to regulate their autophagic degradation and adaptation to stress during development.

Previous studies from Dr. ZHANG Hong’s lab have shown that the P granule components, PGL-1 and PGL-3, are selectively degraded by autophagy during C. elegans embryogenesis. SEPA-1 acts as the receptor for degradation and formation of PGL-1/-3 granules (Zhang et al., Cell 2009). They further showed that the scaffold protein EPG-2 is also essential for degradation of PGL-1/-3 granules (Tian et al., Cell 2010).  Efficient autophagic removal of PGL-1 and PGL-3 is also controlled by their post-translational arginine methylation, which is mediated by the PRMT1 homolog EPG-11 (Li et al., Mol Cell 2013). Levels of PGL-1, PGL-3, SEPA-1 and EPG-2 also affect the removal of PGL granules (Zhang et al., Autophagy 2017). How these multi-layered regulatory mechanisms act concertedly to mediate efficient removal of diffuse PGL-1 and PGL-3 in somatic cells is poorly understood.


Figure. Phase separation and transition control autophagic degradation of PGL granules.

In this new study, the authors showed that 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. Accumulation of PGL granules is an adaptive response to maintain embryonic viability during heat stress. This work 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.

Dr. ZHANG Hong from the Institute of Biophysics is the corresponding author. Dr. ZHANG Gangming from Dr. ZHANG Hong’s lab is the first author of this paper. Dr. WANG Zheng from the Institute of Biophysics and Dr. DU Zhuo from Institute of Genetics and Developmental Biology also contribute to this work. This work was supported by the Strategic Priority Research Program, CAS, NSFC, National Chinese Ministry of Science and Technology, and the Key Research Program of Frontier Sciences, CAS.

Article link:
https://www.cell.com/cell/fulltext/S0092-8674(18)31022-5?code=cell-site

Contact: ZHANG Hong
Institute of Biophysics, Chinese Academy of Sciences
Beijing 100101, China
Phone: 86-10-64848238
Email: hongzhang@ibp.ac.cn

 

 

 

 

 

 

 

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