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首页> 外文期刊>Journal of Molecular Biology >The reorientation of cell nucleus promotes the establishment of front-rear polarity in migrating fibroblasts
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The reorientation of cell nucleus promotes the establishment of front-rear polarity in migrating fibroblasts

机译：细胞核的重新定向促进成纤维细胞迁移前后极性的建立

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The establishment of cell polarity is an essential step in the process of cell migration. This process requires precise spatiotemporal coordination of signaling pathways that in most cells create the typical asymmetrical profile of a polarized cell with nucleus located at the cell rear and the microtubule organizing center (MTOC) positioned between the nucleus and the leading edge. During cell polarization, nucleus rearward positioning promotes correct microtubule organizing center localization and thus the establishment of front-rear polarity and directional migration. We found that cell polarization and directional migration require also the reorientation of the nucleus. Nuclear reorientation is manifested as temporally restricted nuclear rotation that aligns the nuclear axis with the axis of cell migration. We also found that nuclear reorientation requires physical connection between the nucleus and cytoskeleton mediated by the LINC (linker of nucleoskeleton and cytoskeleton) complex. Nuclear reorientation is controlled by coordinated activity of lysophosphatidic acid (LPA)-mediated activation of GTPase Rho and the activation of integrin, FAK (focal adhesion kinase), Src, and p190RhoGAP signaling pathway. Integrin signaling is spatially induced at the leading edge as FAK and p190RhoGAP are predominantly activated or localized at this location. We suggest that integrin activation within lamellipodia defines cell front, and subsequent FAK, Src, and p190RhoGAP signaling represents the polarity signal that induces reorientation of the nucleus and thus promotes the establishment of front-rear polarity.
机译：细胞极性的建立是细胞迁移过程中必不可少的步骤。此过程需要精确的时空协调信号传导途径，在大多数细胞中会形成极化细胞的典型不对称分布，其细胞核位于细胞后部，微管组织中心（MTOC）位于细胞核与前缘之间。在细胞极化期间，细胞核向后定位可促进正确的微管组织中心定位，从而促进前后极性和方向迁移的建立。我们发现细胞的极化和定向迁移也需要细胞核的重新定向。核重新定向表现为在时间上受限制的核旋转，使核轴与细胞迁移轴对齐。我们还发现，核的重新定向需要由LINC（核骨架与细胞骨架的连接子）复合体介导的核与细胞骨架之间的物理连接。核的重新定向受溶血磷脂酸（LPA）介导的GTPase Rho激活和整联蛋白，FAK（黏着斑激酶），Src和p190RhoGAP信号通路激活的控制。由于FAK和p190RhoGAP主要在此位置激活或定位，因此整合素信号传导在前沿被空间诱导。我们建议在lamellipodia中的整联蛋白激活定义细胞前沿，随后的FAK，Src和p190RhoGAP信号代表极性信号，该信号诱导细胞核的重新定向，从而促进前后极性的建立。

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