Nuclear Actin Network Assembly by Formins Regulates the SRF Coactivator MAL
Nuclear Actin Network Assembly by Formins Regulates the SRF Coactivator MAL
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DOI：
10.1126/science.1235038
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发表时间：
2013-05-17
期刊：
影响因子：
56.9
通讯作者：
Grosse, Robert
中科院分区：
文献类型：
--
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
形成蛋白是细胞质中肌动蛋白丝组装的有效激活剂。反过来，细胞质肌动蛋白聚合可以促进肌动蛋白从巨核细胞急性白血病（MAL）蛋白中释放，用于血清反应因子（SRF）转录活性。我们发现，formins聚合肌动蛋白内的哺乳动物细胞核驱动血清依赖的MAL-SRF活动。血清刺激细胞核内的肌动蛋白丝在一个formin依赖的方式快速组装。用光遗传学工具调节内源性β-Dia，其允许核β-Dia自抑制的光反应性释放。活化的mDia促进快速和可逆的核肌动蛋白网络组装，随后的MAL核积累和SRF活性。因此，细胞核内的动态聚合肌动蛋白结构是血清反应的一部分。
Formins are potent activators of actin filament assembly in the cytoplasm. In turn, cytoplasmic actin polymerization can promote release of actin from megakaryocytic acute leukemia (MAL) protein for serum response factor (SRF) transcriptional activity. We found that formins polymerized actin inside the mammalian nucleus to drive serum-dependent MAL-SRF activity. Serum stimulated rapid assembly of actin filaments within the nucleus in a formin-dependent manner. The endogenous formin mDia was regulated with an optogenetic tool, which allowed for photoreactive release of nuclear formin autoinhibition. Activated mDia promoted rapid and reversible nuclear actin network assembly, subsequent MAL nuclear accumulation, and SRF activity. Thus, a dynamic polymeric actin structure within the nucleus is part of the serum response.