BAF is required for emerin assembly into the reforming nuclear envelope.
BAF is required for emerin assembly into the reforming nuclear envelope.
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发表时间：
2001-12
影响因子：
4
通讯作者：
T. Haraguchi;T. Koujin;M. Segura-Totten;Kenneth K. Lee;Y. Matsuoka;Y. Yoneda;K. Wilson;Y. Hiraoka
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作者：
T. Haraguchi;T. Koujin;M. Segura-Totten;Kenneth K. Lee;Y. Matsuoka;Y. Yoneda;K. Wilson;Y. Hiraoka
Emerin突变导致Emery-Dreifuss肌营养不良症（EDMD）的X连锁隐性形式。Emerin在间期定位于核被膜（NE）的内膜，并在有丝分裂期间当NE分解时扩散到ER中。我们分析了野生型和突变GFP标记的Emerin蛋白在活的HeLa细胞核膜组装过程中的招聘。在分裂末期，Emerin在分裂末期染色体的“核心”区域短暂积累，随后分布在整个核边缘。自整合屏障因子（BAF）是一种在体外与双链DNA非特异性结合的蛋白质，在分裂末期与emerin共定位于染色体的“核心”区域。一个emerin突变体缺陷结合BAF在体外未能本地化的“核心”在体内，随后未能本地化的改革NE。在HeLa细胞表达BAF突变体G25 E，这并没有显示出“核心”的本地化，内源性emerin蛋白未能本地化的“核心”区域在末期，并没有组装成NE在随后的间期。BAF突变体G25 E也能使LAP 2 β和核纤层蛋白A从NE上明显移位，但对核纤层蛋白B的定位没有影响。我们的结论是，BAF是必需的emerin和A-型lamins在重组NE在末期的组装，并可能介导其稳定性在随后的间期。
Mutations in emerin cause the X-linked recessive form of Emery-Dreifuss muscular dystrophy (EDMD). Emerin localizes at the inner membrane of the nuclear envelope (NE) during interphase, and diffuses into the ER when the NE disassembles during mitosis. We analyzed the recruitment of wildtype and mutant GFP-tagged emerin proteins during nuclear envelope assembly in living HeLa cells. During telophase, emerin accumulates briefly at the 'core' region of telophase chromosomes, and later distributes over the entire nuclear rim. Barrier-to-autointegration factor (BAF), a protein that binds nonspecifically to double-stranded DNA in vitro, co-localized with emerin at the 'core' region of chromosomes during telophase. An emerin mutant defective for binding to BAF in vitro failed to localize at the 'core' in vivo, and subsequently failed to localize at the reformed NE. In HeLa cells that expressed BAF mutant G25E, which did not show 'core' localization, the endogenous emerin proteins failed to localize at the 'core' region during telophase, and did not assemble into the NE during the subsequent interphase. BAF mutant G25E also dominantly dislocalized LAP2beta and lamin A from the NE, but had no effect on the localization of lamin B. We conclude that BAF is required for the assembly of emerin and A-type lamins at the reforming NE during telophase, and may mediate their stability in the subsequent interphase.