CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

作者：Xiaoqiang Liu, Jinrui Yang, Meng Kong, Min Jiang, Luojia Liu, Jinghong Zhang, Jinghong Zhang, Xu Chen, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jie Liu, Ping Zhang, Ping Zhang · 发表于：Burns & Trauma · 年份：2023 · DOI：10.1093/burnst/tkad012 · 被引用次数：8 · 研究领域：Planarian Biology and Electrostimulation、Microbial Inactivation Methods、Wnt/β-catenin signaling in development and cancer

Background: Endogenous electric fields (EFs) play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound healing. Although polarization of leadercells is essential for collective migration, the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain unclear. This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets. Methods: Collective migration of the human epidermal monolayer (human immortalized keratinocytes HaCaT) under EFs was observed via time-lapse microscopy. The involvement of tetraspanin-29 (CD9) in EF-induced fibrous actin (F-actin) polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic manipulation. Blocking, rescue and co-culture experiments were conducted to explore the downstream signalling of CD9. Results: EFs guided the coordinated collective migration of the epithelial monolayer to the anode, with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration. F-actin polarization, as expected, played an essential role in pseudopod formation in leader cells under EFs. By confocal microscopy, we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs. Interestingly, g...