温古林的机械敏感招募维持了在上皮三细胞结处的结合完整性和屏障功能
Lotte van den Goor1, Jolene Iseler1, Katherine M Koning2
1Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 1105 North University Avenue, Ann Arbor, MI 48109, USA.
Current biology : CB
|September 28, 2024
概括
文库林在三细胞结点 (TCJs) 定了actomyosin网络,维持了上皮屏障的功能. 温古林的损失破坏了TCJ的完整性,并增加了屏障泄漏,突出了它在细胞粘附和透性中的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 皮质生物学 皮质生物学
- 机械生物学 机械生物学
背景情况:
- 状细胞-细胞结合点,包括附着细胞和紧密结合点,对于上皮质完整性和选择性透性至关重要.
- 三细胞结 (TCJs) 代表了三个细胞相遇的独特地点,为维持屏障功能提出了独特的挑战.
- 在维护TCJ完整性和屏障功能方面,阿克托米奥辛介导的张力作用仍然不完全理解.
研究的目的:
- 阐明在TCJ中传递和维持actomyosin张力的机制.
- 研究机械敏感蛋白Vinculin在定actomyosin网络在TCJs中的作用.
- 确定Vinculin如何影响TCJ完整性和在不同机械张力下屏障功能.
主要方法:
- 利用Xenopus laevis胚胎上皮作为一个体内模型系统.
- 采用光遗传学来敏调节节点张力.
- 执行了Vinculin knockdown (KD) 并评估了对actomyosin组织,蛋白质定位 (Angulin-1,ZO-1),actin稳定性 (FRAP) 和屏障功能 (实时成像测定) 的影响.
主要成果:
- 温古林在增加张力时,机械敏感地被招募到围绕TCJs的顶峰连接处.
- 文库林KD导致TCJs的actomyosin下降和混乱,减少了actin稳定性,并破坏了Angulin-1的稳定性.
- 文库林KD损害了TCJ的完整性和屏障功能,由破坏的F-actin,ZO-1信号中断和增加的屏障泄漏,特别是高压下,证明了这一点.
结论:
- 温古林对于在TCJ中定actomyosin网络至关重要,从而保持其完整性和屏障功能.
- 温古林介导的actomyosin组织在调节TCJ的粘附和屏障功能之间的相互作用方面发挥着至关重要的作用.
- 这项研究揭示了一种新的机制,即如何在TCJ中集成机械力,以确保上皮质平衡.
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