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-catenin酸化在线粒分裂过程中升高,以抵抗顶端圆和上皮屏障泄漏
Phuong M Le1, Jeanne M Quinn1,2, Annette S Flozak1
1Department of Pulmonary Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
bioRxiv : the preprint server for biology
|September 16, 2024
概括
线粒分裂期间的上皮细胞分裂涉及α-catenin酸化,这抑制了细胞圆化,并加强了细胞-细胞相互作用,以维持上皮屏障功能.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 皮质生物学 皮质生物学
背景情况:
- 表皮屏障的功能依赖于附着结,特别是α-catenin在将cadherins与actin细胞骨结合中的作用.
- α-catenin的机械敏感展开对其功能至关重要,其酸化状态,特别是在P-链接器区域,与细胞过程有关.
- 驱动α-catenin酸化的特定细胞事件在很大程度上是未知的.
研究的目的:
- 为了研究化过程中α-catenin酸化在维持上皮质屏障功能的作用.
- 为了确定当α-catenin酸化达到最大时的特定线粒分裂阶段.
- 阐明α-catenin酸化如何影响细胞形状和细胞分裂期间的细胞相互作用.
主要方法:
- 对已公布的蛋白质组数据集进行分析,以确定线粒分裂期间的α-catenin酸化水平.
- 用野生型,基突变型和基仿真型的α-catenin重组CRISPR-Cas9淘汰MDCK细胞.
- 显微镜和生物物理测试以评估细胞圆形,细胞相互作用和上皮屏障完整性.
主要成果:
- 在线化过程中,α-catenin的P-链区域被最大限度的酸化.
- 阿尔法-素的完全酸化限制了线粒分裂期间的尖端细胞圆形化.
- 这种酸化增强了分裂和不分裂的邻近细胞之间的相互作用,从而限制了上皮屏障的泄漏.
结论:
- 线性细胞分裂触发最大的α-catenin酸化,这对于维持表皮屏障功能至关重要.
- 酸化抑制了细胞圆形化,并增强了细胞分裂期间的细胞粘附,防止屏障破坏.
- 表皮细胞分裂作为研究在形态遗传过程中结合复合体协调调节的模型系统.
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