Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis
Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis
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DOI：
10.1016/j.yexcr.2007.05.023
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发表时间：
2007-11-15
影响因子：
3.7
通讯作者：
Schwartz, Lawrence M.
中科院分区：
文献类型：
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作者：
Gao, Zheng-Liany;Deblis, Ryan;Schwartz, Lawrence M.
Hic-5 是粘着斑蛋白桩蛋白超家族的仅 LIM 成员。它已被证明可以调节一系列生物过程，包括：衰老、肿瘤发生、类固醇激素作用、整合素信号传导、分化和细胞凋亡。为了更好地了解 Hic-5 在发育过程中的作用，我们对 C2C12 成肌细胞（一种成熟的肌生成模型）中的 Hic-5 表达和功能进行了详细分析。我们发现：（1）成肌细胞表达至少6种不同的Hic-5亚型； (2) 两种主要亚型 Hic-5 α 和 Hic-5 β 在肌生成过程中存在差异表达； (3)任何实验诱导的Hic-5表达变化都会导致分化过程中细胞凋亡的大幅增加； (4) Hic-5 α的异位表达允许分化，而Hic-5 β或反义Hic-5的表达则阻断成肌细胞融合，但不阻断化疗分化； (5) Hic-5定位于C2C12成肌细胞的粘着斑，Hic-5的扰动导致细胞铺展缺陷； (6) Hic-5表达的改变干扰层粘连蛋白表达的正常动态； (7)异位层粘连蛋白，但不是纤连蛋白，可以挽救Hic-5诱导的成肌细胞存活和分化阻断。我们的数据证明了各个 Hic-5 亚型在肌生成过程中的不同作用，并支持 Hic-5 通过整合素信号传导介导这些作用的假设。 (C) 2007 Elsevier Inc. 保留所有权利。
Hic-5 is a LIM-only member of the paxillin superfamily of focal adhesion proteins. It has been shown to regulate a range of biological processes including: senescence, tumorigenesis, steroid hormone action, integrin signaling, differentiation, and apoptosis. To better understand the roles of Hic-5 during development, we initiated a detailed analysis of Hic-5 expression and function in C2C12 myoblasts, a well-established model for myogenesis. We have found that: (1) myoblasts express at least 6 distinct Hic-5 isoforms; (2) the two predominant isoforms, Hic-5 alpha and Hic-5 beta, are differentially expressed during myogenesis; (3) any experimentally induced change in Hic-5 expression results in a substantial increase in apoptosis during differentiation; (4) ectopic expression of Hic-5 alpha is permissive to differentiation while expression of either Hic-5 beta or antisense Hic-5 blocks myoblast fusion but not chemo differentiation; (5) Hic-5 localizes to focal adhesions in C2C12 myoblasts and perturbation of Hic-5 leads to defects in cell spreading; (6) alterations in Hic-5 expression interfere with the normal dynamics of laminin expression; and (7) ectopic laminin, but not fibronectin, can rescue the Hic-5-induced blockade of myoblast survival and differentiation. Our data demonstrate differential roles for individual Hic-5 isoforms during myogenesis and support the hypothesis that Hic-5 mediates these effects via integrin signaling. (C) 2007 Elsevier Inc. All rights reserved.