Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation (ZMBE), Cells in Motion Interfaculty Center, University of Münster, 48149, Münster, Germany.
Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), University of Münster, 48149, Münster, Germany.
Adv Sci (Weinh). 2023 May;10(13):e2300244. doi: 10.1002/advs.202300244. Epub 2023 Mar 20.
The plasma membrane of a cell is subject to stresses causing ruptures that must be repaired immediately to preserve membrane integrity and ensure cell survival. Yet, the spatio-temporal membrane dynamics at the wound site and the source of the membrane required for wound repair are poorly understood. Here, it is shown that early endosomes, previously only known to function in the uptake of extracellular material and its endocytic transport, are involved in plasma membrane repair in human endothelial cells. Using live-cell imaging and correlative light and electron microscopy, it is demonstrated that membrane injury triggers a previously unknown exocytosis of early endosomes that is induced by Ca entering through the wound. This exocytosis is restricted to the vicinity of the wound site and mediated by the endosomal soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) VAMP2, which is crucial for efficient membrane repair. Thus, the newly identified Ca -evoked and localized exocytosis of early endosomes supplies the membrane material required for rapid resealing of a damaged plasma membrane, thereby providing the first line of defense against damage in mechanically challenged endothelial cells.
细胞膜会受到导致破裂的压力，必须立即修复，以保持膜的完整性并确保细胞存活。然而，伤口部位的膜时空动力学以及修复伤口所需的膜的来源仍知之甚少。本文表明，早期内涵体以前仅在细胞外物质摄取及其胞吞运输中发挥作用，在人内皮细胞的质膜修复中发挥作用。通过活细胞成像和相关的光和电子显微镜，证明了膜损伤会触发早期内涵体的一种未知的胞吐作用，该作用是由伤口处进入的 Ca 所诱导的。这种胞吐作用仅限于伤口部位附近，并且由内涵体可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）VAMP2 介导，这对于有效的膜修复至关重要。因此，新发现的 Ca 触发的和局部化的早期内涵体胞吐作用为迅速封闭受损质膜提供了所需的膜材料，从而为机械性挑战的内皮细胞提供了第一道防线。
