Mind bomb 2 promotes cell migration and epithelial structure by regulating adhesion complexes and the actin cytoskeleton
Mind bomb 2 promotes cell migration and epithelial structure by regulating adhesion complexes and the actin cytoskeleton
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DOI：
10.1016/j.ydbio.2022.08.009
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发表时间：
2022-09-17
影响因子：
2.7
通讯作者：
Starz-Gaiano，Michelle
中科院分区：
文献类型：
--
作者：
Trivedi，Sunny;Bhattacharya，Mallika;Starz-Gaiano，Michelle
细胞迁移在动物发育中是必不可少的，在转移和炎症性疾病中也参与其中。一些细胞集体迁移，这要求它们在上皮性特征(如稳定的细胞-细胞粘附性)和运动性特征(如粘附性快速周转和动态细胞骨架结构)之间取得平衡。这是如何监管的，目前尚不完全清楚，但了解这一点很重要。在研究果蝇发生的过程中，我们发现E3泛素连接酶，即心灵炸弹2(Mind Bomb 2，MIB2)，是促进上皮细胞稳定性和边缘细胞集体迁移所必需的。通过生化分析，我们鉴定了MIB2复合体的组成成分，包括E-钙粘蛋白和α-和β-连环蛋白，以及肌动蛋白调节因子。我们还发现三种MIB2相互作用的蛋白，RhoGAP19D，超绒毛蛋白和肌球蛋白重链样，影响边缘细胞的迁移。mib2突变的主体毛囊细胞显著减少了基于E-钙粘附素的黏附复合体，并减少了肌动蛋白细丝。我们的结论是，MIB2起到稳定E-钙粘附素为基础的黏附复合体的作用，并促进一个强大的肌动蛋白细胞骨架网络，这对维持上皮细胞的完整性是重要的。与钙粘附素、黏附复合体和其他细胞骨架调节因子的相互作用有助于其在集体细胞迁移中的作用。由于MIB2的保守性很好，它在其他生物中可能具有类似的功能意义。
Cell migration is essential in animal development and co-opted during metastasis and inflammatory diseases. Some cells migrate collectively, which requires them to balance epithelial characteristics such as stable cell-cell adhesions with features of motility like rapid turnover of adhesions and dynamic cytoskeletal structures. How this is regulated is not entirely clear but important to understand. While investigatingDrosophilaoogenesis, we found that the putative E3 ubiquitin ligase, Mind bomb 2 (Mib2), is required to promote epithelial stability and the collective cell migration of border cells. Through biochemical analysis, we identified components of Mib2 complexes, which include E-cadherin and α- and β-catenins, as well as actin regulators. We also found that three Mib2 interacting proteins, RhoGAP19D, Supervillin, and Myosin heavy chain-like, affect border cell migration.mib2mutant main body follicle cells have drastically reduced E-cadherin-based adhesion complexes and diminished actin filaments. We conclude that Mib2 acts to stabilize E-cadherin-based adhesion complexes and promote a robust actin cytoskeletal network, which is important for maintenance of epithelial integrity. The interaction with cadherin adhesion complexes and other cytoskeletal regulators contribute to its role in collective cell migration. Since Mib2 is well conserved, it may have similar functional significance in other organisms.