Maintaining the integrity of the plasma membrane after cellular damage is essential for cell survival. However, it is unclear how cells repair large membrane injuries in vivo. Here, we report that the tetraspanin protein, TSP-15, is recruited to large membrane wounds and forms a ring-like structure in C. elegans epidermis and promotes membrane repair after an injury. TSP-15 recruits from the adjacent region underneath the plasma membrane to the wound site in a RAB-5-dependent manner upon membrane damage. Genetic and live-imaging analysis suggested that the endosomal sorting complex required for transport III (ESCRT III) is necessary for recruiting TSP-15 from the early endosome to the damaged membrane. Moreover, TSP-15 interacts with and is required for the accumulation of t-SNARE protein Syntaxin-2, which facilitates membrane repair. These findings provide valuable insights into the role of the conserved tetraspanin TSP-15 in the cellular repair of large wounds resulting from environmental insults.

在细胞损伤后保持质膜的完整性对于细胞存活至关重要。然而，尚不清楚细胞如何在体内修复大膜损伤。在这里，我们报告了四跨膜蛋白 TSP-15 被招募到大的膜伤口并在秀丽隐杆线虫中形成环状结构表皮并促进损伤后的膜修复。TSP-15 在膜损伤时以 RAB-5 依赖性方式从质膜下方的相邻区域募集到伤口部位。遗传和实时成像分析表明，运输 III (ESCRT III) 所需的内体分选复合物对于将 TSP-15 从早期内体募集到受损膜是必需的。此外，TSP-15 与促进膜修复的 t-SNARE 蛋白 Syntaxin-2 相互作用并且是其积累所必需的。这些发现为保守的四跨膜蛋白 TSP-15 在由环境损伤引起的大伤口的细胞修复中的作用提供了有价值的见解。