Raj Nikita, Weiß Martin S, Vos Bart E, Weischer Sarah, Brinkmann Frauke, Betz Timo, Trappmann Britta, Gerke Volker
Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation (ZMBE), Multiscale Imaging Centre, Cells in Motion Interfaculty Center, University of Münster, 48149, Münster, Germany.
Bioactive Materials Laboratory, Max Planck Institute for Molecular Biomedicine, 48149, Münster, Germany.
Adv Sci (Weinh). 2024 Dec;11(48):e2402317. doi: 10.1002/advs.202402317. Epub 2024 Oct 3.
Disruptions of the eukaryotic plasma membrane due to chemical and mechanical challenges are frequent and detrimental and thus need to be repaired to maintain proper cell function and avoid cell death. However, the cellular mechanisms involved in wound resealing and restoration of homeostasis are diverse and contended. Here, it is shown that clathrin-mediated endocytosis is induced at later stages of plasma membrane wound repair following the actual resealing of the wound. This compensatory endocytosis occurs near the wound, predominantly at sites of previous early endosome exocytosis which is required in the initial stage of membrane resealing, suggesting a spatio-temporal co-ordination of exo- and endocytosis during wound repair. Using cytoskeletal alterations and modulations of membrane tension and membrane area, membrane tension is identified as a major regulator of the wounding-associated exo- and endocytic events that mediate efficient wound repair. Thus, membrane tension changes are a universal trigger for plasma membrane wound repair modulating the exocytosis of early endosomes required for resealing and subsequent clathrin-mediated endocytosis acting at later stages to restore cell homeostasis and function.
由于化学和机械刺激导致的真核细胞质膜破坏频繁发生且具有危害性,因此需要进行修复以维持细胞的正常功能并避免细胞死亡。然而,参与伤口重新封闭和内环境稳态恢复的细胞机制多种多样且存在争议。本文表明,网格蛋白介导的内吞作用在质膜伤口修复的后期、伤口实际重新封闭之后被诱导。这种补偿性内吞作用发生在伤口附近,主要发生在先前早期内体胞吐作用的位点,而早期内体胞吐作用在膜重新封闭的初始阶段是必需的,这表明在伤口修复过程中胞吐作用和内吞作用存在时空协调。利用细胞骨架改变以及膜张力和膜面积的调节,膜张力被确定为介导有效伤口修复的与伤口相关的胞吐和内吞事件的主要调节因子。因此,膜张力变化是质膜伤口修复的普遍触发因素,它调节重新封闭所需的早期内体的胞吐作用以及随后在后期起作用以恢复细胞内环境稳态和功能的网格蛋白介导的内吞作用。