Department of Cell Biology, Yale School of Medicine, 295 Congress Avenue, New Haven, CT, 06520, USA.
Department of Cell Biology, Yale School of Medicine, 295 Congress Avenue, New Haven, CT, 06520, USA.
Curr Opin Cell Biol. 2020 Jun;64:25-33. doi: 10.1016/j.ceb.2020.01.011. Epub 2020 Feb 24.
Understanding how the integrity of the nuclear membranes is protected against internal and external stresses is an emergent challenge. Work reviewed here investigated the mechanisms by which losses of nuclear-cytoplasmic compartmentalization are sensed and ameliorated. Fundamental to these is spatial control over interactions between the endosomal sorting complexes required for transport machinery and LAP2-emerin-MAN1 family inner nuclear membrane proteins, which together promote nuclear envelope sealing in interphase and at the end of mitosis. We suggest that the size of the nuclear envelope hole dictates the mechanism of its repair, with larger holes requiring barrier-to-autointegration factor and the potential triggering of a postmitotic nuclear envelope reassembly pathway in interphase. We also consider why these mechanisms fail at ruptured micronuclei. Together, this work re-emphasizes the need to understand how membrane flow and local lipid metabolism help ensure that the nuclear envelope is refractory to mechanical rupture yet fluid enough to allow its essential dynamics.
理解核膜完整性如何抵御内外压力是一个新出现的挑战。本文综述了研究核质区室化丧失如何被感知和改善的机制。其中的基本原理是，对内核膜蛋白 LAP2-emerin-MAN1 家族与内体分选复合物必需运输机器之间相互作用的空间控制，共同促进有丝分裂间期和末期核膜的封闭。我们认为核膜孔的大小决定了其修复的机制，较大的孔需要屏障整合因子和潜在的有丝分裂后核膜重装配途径的触发。我们还考虑了为什么这些机制在破裂的微核中失效。总的来说，这项工作再次强调了需要理解膜流和局部脂质代谢如何帮助确保核膜不易发生机械破裂，同时又足够灵活以允许其基本动力学。
