Ji Julie Y, Lee Richard T, Vergnes Laurent, Fong Loren G, Stewart Colin L, Reue Karen, Young Stephen G, Zhang Qiuping, Shanahan Catherine M, Lammerding Jan
Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts 02139, USA.
J Biol Chem. 2007 Jul 6;282(27):20015-26. doi: 10.1074/jbc.M611094200. Epub 2007 May 8.
Mutations of the nuclear lamins cause a wide range of human diseases, including Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome. Defects in A-type lamins reduce nuclear structural integrity and affect transcriptional regulation, but few data exist on the biological role of B-type lamins. To assess the functional importance of lamin B1, we examined nuclear dynamics in fibroblasts from Lmnb1(Delta/Delta) and wild-type littermate embryos by time-lapse videomicroscopy. Here, we report that Lmnb1(Delta/Delta) cells displayed striking nuclear rotation, with approximately 90% of Lmnb1(Delta/Delta) nuclei rotating at least 90 degrees during an 8-h period. The rotation involved the nuclear interior as well as the nuclear envelope. The rotation of nuclei required an intact cytoskeletal network and was eliminated by expressing lamin B1 in cells. Nuclear rotation could also be abolished by expressing larger nesprin isoforms with long spectrin repeats. These findings demonstrate that lamin B1 serves a fundamental role within the nuclear envelope: anchoring the nucleus to the cytoskeleton.
核纤层蛋白的突变会引发多种人类疾病,包括埃默里-德雷福斯肌营养不良症和哈钦森-吉尔福德早衰综合征。A型核纤层蛋白的缺陷会降低核结构的完整性并影响转录调控,但关于B型核纤层蛋白的生物学作用的数据却很少。为了评估核纤层蛋白B1的功能重要性,我们通过延时视频显微镜观察了Lmnb1(Delta/Delta)和野生型同窝胚胎成纤维细胞中的核动态变化。在此,我们报告称,Lmnb1(Delta/Delta)细胞表现出显著的核旋转,在8小时内约90%的Lmnb1(Delta/Delta)细胞核至少旋转了90度。这种旋转涉及核内部以及核膜。细胞核的旋转需要完整的细胞骨架网络,并且通过在细胞中表达核纤层蛋白B1可以消除这种旋转。通过表达具有长血影蛋白重复序列的更大的nesprin异构体也可以消除核旋转。这些发现表明,核纤层蛋白B1在核膜中起着基本作用:将细胞核锚定到细胞骨架上。