12月17日水木清华生命科学讲座系列第97期 - 张宏
时间:2020-12-17 15:00-16:00
主讲人:张宏
主题:Liquid–liquid phase separation in autophagy
地点:生物新馆143
Brief CV
Dr. Hong Zhang is an Investigator in the Institute of Biophysics, Chinese Academy of Sciences. He graduated from Albert Einstein College of Medicine and had his postdoc training in the MGH Cancer Center, Harvard Medical School. Zhang’s lab demonstrated that during C. elegans embryogenesis, specialized protein aggregates, called PGL granules, are removed by autophagy in somatic cells. Using this as a model, his lab performed the first systematic genetic screens for novel autophagy genes in higher eukaryotes, resulting in identification of a set of metazoan-specific autophagy genes, known as epg genes. Recently, his lab uncovered that phase separation and transition control autophagic degradation of protein aggregates. The awards he has won in recent years include the Second Prize of The State Natural Science Award (2019), Outstanding Achievement Award of the Chinese Society for Cell Biology (2019), FVIL Scholar (臻溪生命学者) (2018), the 6th C.C.Tan (Jia-Zhen Tan) Life Science Award (2013), National Outstanding Young Scientist Award (2012) and HHMI International Early Career Scientist Award (2012). Dr. Hong Zhang is an Associate Editor for Autophagy and is also on the Editorial Board for Trends in Biochemical Sciences, Journal of Cell Biology, eLife, EMBO reports, JCS and Cell Death & Differentiation.
Abstract
Liquid–liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into distinct condensates. Liquid-like condensates can transition into gel and solid states, which are essential for fulfilling their different functions. One function of LLPS is to triage protein substrates into condensates for selective autophagic degradation. My group demonstrated that a specialized type of protein condensate, the PGL granule, is degraded by autophagy during C. elegans embryogenesis. Degradation of PGL granules requires the concerted actions of the receptor protein SEPA-1, the scaffold protein EPG-2, and various post-translational modifications (PTMs). We demonstrated that PGL granules are assembled via LLPS. The size and biophysical properties of PGL granules, which are controlled by SEPA-1, EPG-2 and PTMs, determine their susceptibility to autophagic degradation. mTORC1-mediated phosphorylation modulates LLPS of PGL granules, enabling them to evade surveillance by the autophagic machinery, and consequently increasing embryonic viability under heat stress conditions. We also found that LLPS of the transcription factor TFEB is involved in its activation of the expression of genes involved in autophagy and lysosomal function and biogenesis. Modulation of LLPS of TFEB thus provides another layer of regulatory mechanisms for degradation of protein aggregates.