Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly

Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly
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DOI:
10.1038/sj.emboj.7601470
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发表时间:
2007-01-10
期刊:
影响因子:
11.4
通讯作者:
Mattaj, Iain W.
Mattaj, Iain W.
中科院分区:
生物学1区
文献类型:
--
作者:
Gorjanacz, Matyas;Klerkx, Elke P. F.;Mattaj, Iain W.

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自整合障碍因子(BAF)是一种重要的、高度保守的后生动物蛋白。BAF与内核膜的LEM(LAP 2,emerin,MAN 1)结构域携带蛋白相互作用。我们分析了BAF在秀丽隐杆线虫胚胎中的体内功能,使用RNA干扰和温度敏感的baf-1基因突变,发现BAF直接参与核膜(NE)的形成。NE缺陷观察独立的染色质组织表型之前,BAF耗尽蠕虫和苍蝇。我们确定了牛痘相关激酶(VRK)作为BAF磷酸化和定位的调节因子。VRK以细胞周期依赖性方式定位于NE和染色质。VRK的缺失导致几种有丝分裂缺陷,包括NE形成受损和BAF离域。我们认为,VRK磷酸化BAF在NE形成过程中BAF与染色质和核膜蛋白的结合中起着重要的调节作用。
Barrier-to-autointegration factor (BAF) is an essential, highly conserved, metazoan protein. BAF interacts with LEM (LAP2, emerin, MAN1) domain-carrying proteins of the inner nuclear membrane. We analyzed the in vivo function of BAF in Caenorhabditis elegans embryos using both RNA interference and a temperature-sensitive baf-1 gene mutation and found that BAF is directly involved in nuclear envelope (NE) formation. NE defects were observed independent of and before the chromatin organization phenotype previously reported in BAF-depleted worms and flies. We identified vaccinia-related kinase (VRK) as a regulator of BAF phosphorylation and localization. VRK localizes both to the NE and chromatin in a cell-cycle-dependent manner. Depletion of VRK results in several mitotic defects, including impaired NE formation and BAF delocalization. We propose that phosphorylation of BAF by VRK plays an essential regulatory role in the association of BAF with chromatin and nuclear membrane proteins during NE formation.