Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112.
Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Mol Biol Cell. 2022 Nov 1;33(13):ar117. doi: 10.1091/mbc.E22-05-0189. Epub 2022 Aug 31.
Assembly of the nucleus following mitosis requires rapid and coordinate recruitment of diverse constituents to the inner nuclear membrane. We have identified an unexpected role for the nucleoporin Nup153 in promoting the continued addition of a subset of nuclear envelope (NE) proteins during initial expansion of nascent nuclei. Specifically, disrupting the function of Nup153 interferes with ongoing addition of B-type lamins, lamin B receptor, and SUN1 early in telophase, after the NE has initially enclosed chromatin. In contrast, effects on lamin A and SUN2 were minimal, pointing to differential requirements for the ongoing targeting of NE proteins. Further, distinct mistargeting phenotypes arose among the proteins that require Nup153 for NE targeting. Thus, disrupting the function of Nup153 in nuclear formation reveals several previously undescribed features important for establishing nuclear architecture: 1) a role for a nuclear basket constituent in ongoing recruitment of nuclear envelope components, 2) two functionally separable phases of NE formation in mammalian cells, and 3) distinct requirements of individual NE residents for continued targeting during the expansion phase of NE reformation.
有丝分裂后核的组装需要快速协调地将各种成分募集到内核膜上。我们发现核孔蛋白 Nup153 具有一个意想不到的作用，即在核膜最初包围染色质后，在有丝分裂末期，促进核被膜 (NE) 蛋白的持续添加。具体来说，破坏 Nup153 的功能会干扰 B 型核纤层蛋白、核纤层蛋白受体和 SUN1 的持续添加，这发生在 NE 最初包裹染色质之后。相比之下，对核纤层蛋白 A 和 SUN2 的影响最小，这表明持续靶向 NE 蛋白的需求存在差异。此外，在需要 Nup153 进行 NE 靶向的蛋白质中，出现了不同的靶向错误表型。因此，破坏核形成过程中 Nup153 的功能揭示了一些建立核架构的重要的、之前未描述的特征：1）核篮状结构成分在核被膜成分的持续募集中的作用，2）哺乳动物细胞中核形成的两个功能可分离的阶段，以及 3）在核膜重新形成的扩展阶段，单个核被膜居民持续靶向的不同需求。
