The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, London SE1 1UL, UK.
Institute for Cell Biology, Biocenter, Medical University of Innsbruck, Innrain 80/82, A-6020, Innsbruck, Austria.
Dev Cell. 2020 Apr 6;53(1):27-41.e6. doi: 10.1016/j.devcel.2020.01.028. Epub 2020 Feb 27.
Eukaryotic genomes are organized within the nucleus through interactions with inner nuclear membrane (INM) proteins. How chromatin tethering to the INM is controlled in interphase and how this process contributes to subsequent mitotic nuclear envelope (NE) remodeling remains unclear. We have probed these fundamental questions using the fission yeast Schizosaccharomyces japonicus, which breaks and reforms the NE during mitosis. We show that attachments between heterochromatin and the transmembrane Lem2-Nur1 complex at the INM are remodeled in interphase by the ESCRT-III/Vps4 machinery. Failure of ESCRT-III/Vps4 to release Lem2-Nur1 from heterochromatin leads to persistent association of chromosomes with the INM throughout mitosis. At mitotic exit, such trapping of Lem2-Nur1 on heterochromatin prevents it from re-establishing nucleocytoplasmic compartmentalization. Our work identifies the Lem2-Nur1 complex as a substrate for the nuclear ESCRT machinery and explains how the dynamic tethering of chromosomes to the INM is linked to the establishment of nuclear compartmentalization.
真核生物基因组通过与核内 膜（INM）蛋白的相互作用在细胞核内进行组织。在 间期，染色质如何与 INM 连接被控制，以及这个过程如何促进随后的有丝分裂核膜（NE）重塑，目前仍不清楚。我们使用裂殖酵母 Schizosaccharomyces japonicus 探讨了这些基本问题，该酵母在有丝分裂期间会破坏和重建 NE。我们表明，间期通过 ESCRT-III/Vps4 机制重塑了异染色质与 INM 上的跨膜 Lem2-Nur1 复合物之间的连接。如果 ESCRT-III/Vps4 未能将 Lem2-Nur1 从异染色质中释放出来，就会导致染色体在整个有丝分裂过程中与 INM 持续结合。在有丝分裂末期，这种 Lem2-Nur1 在异染色质上的捕获阻止了它重新建立核质区室化。我们的工作确定了 Lem2-Nur1 复合物是核 ESCRT 机制的底物，并解释了染色体与 INM 的动态连接如何与核区室化的建立相关。
