斯克里布尔,Lgl1和肌酸酶IIA与α-/β-catenin相互作用,以保持上皮结的完整性
Maha Abedrabbo1, Shirel Sloomy1, Reham Abu-Leil1
1Department of Biochemistry and Molecular Biology, The Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell adhesion & migration
|September 25, 2023
概括
斯克里布尔和Lgl1蛋白对于通过稳定附着结 (AJs) 来维持上皮细胞粘附至关重要. 它们在TGFβ诱导的EMT期间的下调阻碍了细胞粘附,这表明它们在癌症进展中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 附着结 (AJs) 对于上皮细胞粘附至关重要,涉及E-cadherin-catenin复合体和细胞骨.
- 众所周知,Scribble蛋白可以稳定E-cadherin和catenin的相互作用,但潜在的机制尚不清楚.
研究的目的:
- 阐明Scribble和Lgl1调节附着结合完整性的机制.
- 研究Scribble,Lgl1和NMII-A在上皮细胞粘附和TGFβ诱导的上皮-介质细胞过渡 (EMT) 中的作用.
主要方法:
- 同免疫沉用于识别蛋白质复合体.
- 使用siRNA评估蛋白质功能的耗尽研究.
- 免疫光显微镜用于分析蛋白质定位.
- 西方斑点测试用于评估蛋白质表达和酸化.
主要成果:
- 斯克里布尔,Lgl1和NMII-A与E-cadherin-catenin形成一个复合体.
- 削弱Scribble或Lgl1会破坏E-cadherin-catenin局部化到AJs.
- aPKCζ对Lgl1的酸化控制了Lgl1和E-cadherin-catenin的AJ局部化.
- 斯克里布尔和Lgl1调节NMII-A激活和招募到AJs.
- 在TGFβ诱导的EMT期间,Scribble和Lgl1的下调,它们的再表达抑制了EMT.
结论:
- 斯克里布尔和Lgl1,以及NMII-A,在保持附着结的稳定性方面发挥着至关重要的作用.
- 通过aPKCζ对Lgl1的酸化是AJ局部化的一个关键调节步骤.
- 斯克里布尔和Lgl1通过阻碍TGFβ诱导的EMT进展,作为瘤抑制剂.
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