Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo
Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo
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DOI：
10.1242/jcs.01683
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发表时间：
2005-03-01
影响因子：
4
通讯作者：
Shibanuma, M
中科院分区：
文献类型：
--
作者：
Kim-Kaneyama, J;Suzuki, W;Shibanuma, M
Hic-5是属于桩蛋白LIM家族的一种粘着斑蛋白，穿梭于细胞核内外。在本研究中，我们通过免疫组织化学方法检测了小鼠组织中Hic-5的表达，发现其仅在几种组织的平滑肌细胞中表达。这一结果与先前关于成人组织的报道一致，并且与桩蛋白（与Hic-5最同源的蛋白）相对普遍的表达相矛盾。体内平滑肌细胞的特征之一是器官中持续暴露于机械拉伸。为了研究Hic-5参与细胞对机械应力的反应，我们将小鼠胚胎成纤维细胞暴露于单轴循环拉伸，发现Hic-5在应力期间通过其C-末端LIM结构域从粘着斑重新定位到应力纤维。与此形成鲜明对比的是，桩蛋白没有改变其基于局部粘附的定位。在测试的因素中，包括Hic-5的相互作用伙伴，只有CRP 2（血管平滑肌细胞中表达的唯一LIM蛋白）和GIT 1与Hic-5一样，在循环拉伸过程中定位于应力纤维。有趣的是，Hic-5对包埋在三维胶原凝胶中的细胞的收缩能力显示出抑制作用，并且当CRP 2与Hic-5共定位于这些细胞的纤维结构时，该作用进一步增强。这些结果表明，Hic-5是张力的调解人，移位直接从局灶性粘连肌动蛋白应力纤维后，机械应力和调节细胞的收缩能力的应力纤维。
Hic-5 is a focal adhesion protein belonging to the paxillin LIM family that shuttles in and out of the nucleus. In the present study we examined the expression of Hic-5 among mouse tissues by immunohistochemistry and found its expression only in smooth-muscle cells in several tissues. This result is consistent with a previous report on adult human tissues and contradicts the relatively ubiquitous expression of paxillin, the protein most homologous to Hic-5. One factor characterizing smooth-muscle cells in vivo is a continuous exposure to mechanical stretching in the organs. To study the involvement of Hic-5 in cellular responses to mechanical stress, we exposed mouse embryo fibroblasts to a uni-axial cyclic stretching and found that Hic-5 was relocalized from focal adhesions to stress fibers through its C-terminal LIM domains during the stress. In sharp contrast to this, paxillin did not change its focal-adhesion-based localization. Of the factors tested, which included interacting partners of Hic-5, only CRP2 (an only-LIM protein expressed in vascular smooth-muscle cells) and GIT1 were, like Hic-5, localized to stress fibers during the cyclic stretching. Interestingly, Hic-5 showed a suppressive effect on the contractile capability of cells embedded in three-dimensional collagen gels, and the effect was further augmented when CRP2 co-localized with Hic-5 to fiber structures of those cells. These results suggested that Hic-5 was a mediator of tensional force, translocating directly from focal adhesions to actin stress fibers upon mechanical stress and regulating the contractile capability of cells in the stress fibers.