Comprehensive analysis of formin localization in Xenopus epithelial cells.
Comprehensive analysis of formin localization in Xenopus epithelial cells.
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DOI：
10.1091/mbc.e18-02-0133
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Miller AL
中科院分区：
文献类型：
--
作者：
Higashi T;Stephenson RE;Miller AL
肌动蛋白细胞骨架的重组对细胞过程至关重要，包括胞质分裂和细胞-细胞连接重塑。Formins是保守的过程中的肌动蛋白聚合机器，它通过成核、延长和捆绑线性肌动蛋白细丝来调节肌动蛋白的动态。因为福尔曼家族很大，脊椎动物中至少有15个成员，所以还没有任何全面的研究来检验福尔曼在一种常见细胞类型中的定位和功能。在这里，我们研究了非洲爪哇原肠胚期胚胎上皮细胞中所有15种福尔马林的定位。Dia1和Dia2定位于紧密连接，而Fhod1和Fhod3定位于粘着连接。仅Dia3强定位于细胞动收缩环。Dia1的透明抑制域二聚结构域(DID-DD)区域足以进行Dia1的定位，过表达的Dia1 DID-DD片段竞争性地将Dia1和Dia2从细胞-细胞连接中移除。在Dia1DID-DD过表达的细胞中，Dia1和Dia2错误定位于收缩环，细胞表现出更多的胞质分裂失败。这项工作对所有15种脊椎动物福尔马林在上皮细胞中的定位进行了全面的分析，并认为福尔马林的错误定位会导致上皮细胞胞质分裂失败。
Reorganization of the actin cytoskeleton is crucial for cellular processes, including cytokinesis and cell–cell junction remodeling. Formins are conserved processive actin-polymerizing machines that regulate actin dynamics by nucleating, elongating, and bundling linear actin filaments. Because the formin family is large, with at least 15 members in vertebrates, there have not been any comprehensive studies examining formin localization and function within a common cell type. Here, we characterized the localization of all 15 formins in epithelial cells of Xenopus laevis gastrula-stage embryos. Dia1 and Dia2 localized to tight junctions, while Fhod1 and Fhod3 localized to adherens junctions. Only Dia3 strongly localized at the cytokinetic contractile ring. The Diaphanous inhibitory domain–dimerization domain (DID-DD) region of Dia1 was sufficient for Dia1 localization, and overexpression of a Dia1 DID-DD fragment competitively removed Dia1 and Dia2 from cell–cell junctions. In Dia1 DID-DD–overexpressing cells, Dia1 and Dia2 were mislocalized to the contractile ring, and cells exhibited increased cytokinesis failure. This work provides a comprehensive analysis of the localization of all 15 vertebrate formins in epithelial cells and suggests that misregulated formin localization results in epithelial cytokinesis failure.