Scribble、Lgl1 和肌球蛋白 IIA 与α-/β-连环蛋白相互作用，以维持上皮连接的完整性。
Scribble, Lgl1, and myosin IIA interact with α-/β-catenin to maintain epithelial junction integrity.
机构信息
Department of Biochemistry and Molecular Biology, The Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
出版信息
Cell Adh Migr. 2023 Dec;17(1):1-23. doi: 10.1080/19336918.2023.2260645. Epub 2023 Sep 24.
E-cadherin-catenin complex together with the cytoskeleton, builds the core of Adherens junctions (AJs). It has been reported that Scribble stabilizes the coupling of E-cadherin with catenins promoting epithelial cell adhesion, but the mechanism remains unknown. We show that Scribble, Lgl1, and NMII-A reside in a complex with E-cadherin-catenin complex. Depletion of either Scribble or Lgl1 disrupts the localization of E-cadherin-catenin complex to AJs. aPKCζ phosphorylation of Lgl1 regulates AJ localization of Lgl1 and E-cadherin-catenin complexes. Both Scribble and Lgl1 regulate the activation and recruitment of NMII-A at AJs. Finally, Scribble and Lgl1 are downregulated by TGFβ-induced EMT, and their re-expression during EMT impedes its progression. Our results provide insight into the mechanism regulating AJ integrity by Scribble, Lgl1, and NMII-A.
E-钙黏蛋白-catenin 复合物与细胞骨架一起构成黏着连接（AJs）的核心。有报道称，Scribble 通过稳定 E-钙黏蛋白与连环蛋白的偶联来促进上皮细胞黏附，但具体机制尚不清楚。我们发现 Scribble、Lgl1 和 NMII-A 存在于与 E-钙黏蛋白-catenin 复合物的复合物中。Scribble 或 Lgl1 的缺失会破坏 E-钙黏蛋白-catenin 复合物在 AJs 的定位。aPKCζ 对 Lgl1 的磷酸化调节 Lgl1 和 E-钙黏蛋白-catenin 复合物在 AJs 的定位。Scribble 和 Lgl1 都调节 NMII-A 在 AJs 的激活和募集。最后，TGFβ 诱导的 EMT 会下调 Scribble 和 Lgl1 的表达，而它们在 EMT 期间的重新表达会阻碍 EMT 的进展。我们的研究结果为 Scribble、Lgl1 和 NMII-A 调节 AJ 完整性的机制提供了新的见解。
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