Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J Cell Biol. 2023 Jul 3;222(7). doi: 10.1083/jcb.202205130. Epub 2023 May 18.
Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles. Here, we discovered micrometer-sized worm-shaped ESCRT structures that stably persist for multiple hours at the plasma membrane of macrophages, dendritic cells, and fibroblasts. These structures surround clusters of integrins and known cargoes of extracellular vesicles. The ESCRT structures are tightly connected to the cellular support and are left behind by the cells together with surrounding patches of membrane. The phospholipid composition is altered at the position of the ESCRT structures, and the actin cytoskeleton is locally degraded, which are hallmarks of membrane damage and extracellular vesicle formation. Disruption of actin polymerization increased the formation of the ESCRT structures and cell adhesion. The ESCRT structures were also present at plasma membrane contact sites with membrane-disrupting silica crystals. We propose that the ESCRT proteins are recruited to adhesion-induced membrane tears to induce extracellular shedding of the damaged membrane.
内体分选复合物需要运输（ESCRT）蛋白可以暂时被招募到质膜上进行膜修复和形成细胞外囊泡。在这里，我们发现了微米大小的虫形 ESCRT 结构，这些结构在巨噬细胞、树突状细胞和成纤维细胞的质膜上稳定存在数小时。这些结构包围着整联蛋白簇和细胞外囊泡的已知货物。ESCRT 结构与细胞支架紧密相连，细胞会与周围的膜片一起留下这些结构。ESCRT 结构的位置改变了磷脂成分，肌动蛋白细胞骨架被局部降解，这是膜损伤和细胞外囊泡形成的标志。肌动蛋白聚合的破坏增加了 ESCRT 结构和细胞黏附的形成。ESCRT 结构也存在于与破坏膜的硅晶体的质膜接触部位。我们提出，ESCRT 蛋白被招募到粘附诱导的膜撕裂处以诱导受损膜的细胞外脱落。
