Anillin regulates cell-cell junction integrity by organizing junctional accumulation of Rho-GTP and actomyosin.

Anillin regulates cell-cell junction integrity by organizing junctional accumulation of Rho-GTP and actomyosin.
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DOI:
10.1016/j.cub.2014.04.021
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发表时间:
2014-06-02
期刊:
影响因子:
9.2
通讯作者:
Miller, Ann L.
Miller, Ann L.
中科院分区:
生物学1区
文献类型:
--
作者:
Reyes, Ciara C.;Jin, Meiyan;Breznau, Elaina B.;Espino, Rhogelyn;Delgado-Gonzalo, Ricard;Goryachev, Andrew B.;Miller, Ann L.

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Anillin 是一种支架蛋白,可组织和稳定肌动球蛋白收缩环,以前被认为主要在胞质分裂中发挥作用。使用非洲爪蟾胚胎作为模型系统来检查 Anillin 在完整脊椎动物上皮中的作用,我们发现 Anillin 群体在整个细胞周期中令人惊讶地定位于上皮细胞-细胞连接处,而以前认为它在间期期间位于细胞核中。此外,我们表明 Anillin 在调节细胞-细胞连接完整性方面发挥着关键作用。当 Anillin 被击倒时,紧密连接和粘附连接都会被破坏,导致细胞形状改变和细胞间隙增加。 Anillin 与 Rho、F-肌动蛋白和肌球蛋白 II 相互作用,所有这些因子都调节细胞间连接的结构和功能。当 Anillin 被敲低时,活性 Rho (Rho-GTP)、F-肌动蛋白和肌球蛋白 II 在连接处被错误调节。事实上,在细胞与细胞连接处观察到 Rho-GTP 动态“耀斑”增加,而当 Anillin 耗尽时,连接处 F-肌动蛋白和肌球蛋白 II 的总体积累减少。我们认为 Anillin 是细胞与细胞连接处 Rho-GTP 正确分布以及维持细胞与细胞连接完整性所需的稳健的顶端肌动球蛋白带所必需的。这些结果揭示了 Anillin 在调节上皮细胞-细胞连接中的新作用。
Anillin is a scaffolding protein that organizes and stabilizes actomyosin contractile rings and was previously thought to function primarily in cytokinesis. Using Xenopus laevis embryos as a model system to examine Anillin’s role in the intact vertebrate epithelium, we find that a population of Anillin surprisingly localizes to epithelial cell-cell junctions throughout the cell cycle, whereas it was previously thought to be nuclear during interphase. Further, we show that Anillin plays a critical role in regulating cell-cell junction integrity. Both tight junctions and adherens junctions are disrupted when Anillin is knocked down, leading to altered cell shape and increased intercellular spaces. Anillin interacts with Rho, F-actin, and Myosin II, all of which regulate cell-cell junction structure and function. When Anillin is knocked down, active Rho (Rho-GTP), F-actin, and Myosin II are misregulated at junctions. Indeed, increased dynamic “flares” of Rho-GTP are observed at cell-cell junctions, while overall junctional F-actin and Myosin II accumulation is reduced when Anillin is depleted. We propose that Anillin is required for proper Rho-GTP distribution at cell-cell junctions and for maintenance of a robust apical actomyosin belt, which is required for cell-cell junction integrity. These results reveal a novel role for Anillin in regulating epithelial cell-cell junctions.
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