Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4
Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4
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DOI：
10.1242/jcs.059568
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Takeyasu, Kunio
中科院分区：
文献类型：
--
作者：
Kumeta, Masahiro;Yoshimura, Shige H.;Takeyasu, Kunio
除了众所周知的作为粘着斑处肌动蛋白细丝的交联剂的作用外，肌动蛋白-4还被认为定位于细胞核。在这项研究中，我们揭示了肌动蛋白-4核定位的分子机制及其与转录调控因子的新的相互作用。我们发现，肌动蛋白-4通过核孔复合体以一种不依赖于导入蛋白的方式进入细胞核，并通过依赖于染色体区域维护-1(CRM1)的途径被输出。细胞核肌动蛋白-4水平在G2期晚期显著升高，在G1期显著降低，提示肌动蛋白细胞骨架的主动释放是导致G2期晚期核肌动蛋白-4水平升高的原因。核肌动蛋白-4与INO80染色质重塑复合体相互作用。它还指导细胞周期相关基因的子集的表达，并在M期与依赖上游结合因子(UBF)的rRNA转录机制相互作用。这些发现为不包含核定位信号的蛋白质的核质穿梭和反映细胞骨架形态变化的细胞周期依赖的基因调控提供了分子机制。
In addition to its well-known role as a crosslinker of actin filaments at focal-adhesion sites, actinin-4 is known to be localized to the nucleus. In this study, we reveal the molecular mechanism underlying nuclear localization of actinin-4 and its novel interactions with transcriptional regulators. We found that actinin-4 is imported into the nucleus through the nuclear pore complex in an importin-independent manner and is exported by the chromosome region maintenance-1 (CRM1)-dependent pathway. Nuclear actinin-4 levels were significantly increased in the late G2 phase of the cell cycle and were decreased in the G1 phase, suggesting that active release from the actin cytoskeleton was responsible for increased nuclear actinin-4 in late G2. Nuclear actinin-4 was found to interact with the INO80 chromatin-remodeling complex. It also directs the expression of a subset of cell-cycle-related genes and interacts with the upstream-binding factor (UBF)-dependent rRNA transcriptional machinery in the M phase. These findings provide molecular mechanisms for both nucleocytoplasmic shuttling of proteins that do not contain a nuclear-localization signal and cell-cycle-dependent gene regulation that reflects morphological changes in the cytoskeleton.