近日，德国马克斯·普朗克生物化学研究所的M. S. Hipp等研究组合作发现了核仁起着以相分离的方式进行蛋白质质量控制的作用。相关论文发表在2019年7月26日出版的《科学》杂志上。

核内蛋白质组富含应激敏感蛋白，这提示可能存在高效的蛋白质质控机制来确保构象的维持。研究人员探究了核仁在这一过程中的作用。

在应激条件下培养的哺乳细胞中，错误折叠的蛋白质进入核仁内的颗粒组分（GC）相。与核仁蛋白，例如NPM1，发生短暂的相互作用，使得错误折叠的蛋白移动变缓被控制在液相类似的GC相中，从而避免了不可逆的聚集。当从应激中恢复后，蛋白质的重新折叠与从核仁内的分离依赖于Hsp70。核仁储存错误折叠蛋白的能力是有限的，长期的应激会导致核仁基质不可逆地由液相变为固态，而且质控异常。因此，这项研究表明，核仁具有与分子伴侣类似的性质，并且能够促进核内蛋白在应激下的维护。

附：英文原文

Title: The nucleolus functions as a phase-separated protein quality control compartment

Author: F. Frottin, F. Schueder, S. Tiwary, R. Gupta, R. Krner, T. Schlichthaerle, J. Cox, R. Jungmann, F. U. Hartl, M. S. Hipp

Issue&Volume: Vol 365 Issue 6451

Abstract: The nuclear proteome is rich in stress-sensitive proteins, which suggests that effective protein quality control mechanisms are in place to ensure conformational maintenance. We investigated the role of the nucleolus in this process. In mammalian tissue culture cells under stress conditions, misfolded proteins entered the granular component (GC) phase of the nucleolus. Transient associations with nucleolar proteins such as NPM1 conferred low mobility to misfolded proteins within the liquid-like GC phase, avoiding irreversible aggregation. Refolding and extraction of proteins from the nucleolus during recovery from stress was Hsp70-dependent. The capacity of the nucleolus to store misfolded proteins was limited, and prolonged stress led to a transition of the nucleolar matrix from liquid-like to solid, with loss of reversibility and dysfunction in quality control. Thus, we suggest that the nucleolus has chaperone-like properties and can promote nuclear protein maintenance under stress.

DOI: 10.1126/science.aaw9157

Source: https://science.sciencemag.org/content/365/6451/342