Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion
Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion
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DOI：
10.1016/j.devcel.2014.12.019
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发表时间：
2015-02-09
影响因子：
11.8
通讯作者：
Del Pozo, Miguel A.
中科院分区：
文献类型：
--
作者：
Navarro-Lerida, Inmaculada;Pellinen, Teijo;Del Pozo, Miguel A.
核膜微区被认为可以作为核功能调节的平台，但人们对控制其形成的机制知之甚少。质膜的组织受到肌动蛋白聚合的调节，细胞核中肌动蛋白池的存在表明类似的机制可能在这里发挥作用。我们表明，核膜组织和形态是通过肌动蛋白聚合依赖性机制受活性 Rac1 的核水平调节的。 Rac1 核输出由两个内部核输出信号及其与核磷蛋白-1 (B23) 的相互作用介导，核磷蛋白-1 在细胞核内充当 Rac1 伴侣。 Rac1 核积累改变了细胞质 Rac1 和 Rho 之间的平衡，增加了细胞质中的 RhoA 信号传导并促进高度侵袭性表型。核 Rac1 穿梭是一种精细调节的机制，用于控制核形状和组织以及细胞侵袭性。
Nuclear membrane microdomains are proposed to act as platforms for regulation of nuclear function, but little is known about the mechanisms controlling their formation. Organization of the plasma membrane is regulated by actin polymerization, and the existence of an actin pool in the nucleus suggests that a similar mechanism might operate here. We show that nuclear membrane organization and morphology are regulated by the nuclear level of active Rac1 through actin polymerization-dependent mechanisms. Rac1 nuclear export is mediated by two internal nuclear export signals and through its interaction with nucleophosmin-1 (B23), which acts as a Rac1 chaperone inside the nucleus. Rac1 nuclear accumulation alters the balance between cytosolic Rac1 and Rho, increasing RhoA signaling in the cytoplasm and promoting a highly invasive phenotype. Nuclear Rac1 shuttling is a finely tuned mechanism for controlling nuclear shape and organization and cell invasiveness.