Zhu Hui, Xue Chengbin, Xu Xi, Guo Yibing, Li Xiaohong, Lu Jingjing, Ju Shaoqing, Wang Yongjun, Cao Zheng, Gu Xiaosong
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China.
Cell Death Dis. 2016 Dec 22;7(12):e2523. doi: 10.1038/cddis.2016.441.
Tunneling nanotubes (TNTs) are F-actin-based membrane tubes, and can form between cultured cells and within vital tissues. TNTs mediate intercellular communications that range from electrical signaling to the transfer of organelles. Following peripheral nerve injury, the orchestrated intercellular communications among neural and non-neural cells are required for effective nerve regeneration. It remains unknown whether TNTs exist between neural cells in the peripheral nerve system and how TNTs affect neural regeneration. To address these interesting questions, we investigated the transfer of neurotropic factors, membrane protein, cytoplasmic protein, mitochondria and RNA in functional TNTs formed between cultured Schwann cells (SCs). TNT-like structures were increased not only in cultured SCs after exposure to serum depletion but also in longitudinal sections of proximal sciatic nerve stump harvested after rat peripheral nerve transection. Meanwhile, downregulation of Rab8a or Rab11a in cultured SCs inhibited the formation of functional TNTs and vesicle transfer and led to decrease in cell migration, increase in SCs apoptosis. Likewise, knockdown of Rab8a or Rab11a in primary SCs also suppressed axonal outgrowth from co-cultured dorsal root ganglion (DRG) neurons. Overall, our results suggested that the gene of Rab8a or Rab11a might be involved in the formation of TNTs structures in the peripheral nerve system, while TNTs structures were likely to affect peripheral nerve regeneration through the regulation of neural cell communications.
隧道纳米管（TNTs）是基于丝状肌动蛋白的膜性管道，可在培养的细胞之间以及重要组织内形成。TNTs介导从电信号传导到细胞器转移等多种细胞间通讯。周围神经损伤后，神经细胞与非神经细胞之间协调的细胞间通讯对于有效的神经再生至关重要。目前尚不清楚周围神经系统的神经细胞之间是否存在TNTs以及TNTs如何影响神经再生。为了解决这些有趣的问题，我们研究了培养的雪旺细胞（SCs）之间形成的功能性TNTs中神经营养因子、膜蛋白、细胞质蛋白、线粒体和RNA的转移。不仅在血清饥饿处理后的培养SCs中，而且在大鼠周围神经横断后收获的坐骨神经近端残端的纵切片中，类TNT结构均增加。同时，培养的SCs中Rab8a或Rab11a的下调抑制了功能性TNTs的形成和囊泡转移，并导致细胞迁移减少、SCs凋亡增加。同样，原代SCs中Rab8a或Rab11a的敲低也抑制了共培养的背根神经节（DRG）神经元的轴突生长。总体而言，我们的结果表明，Rab8a或Rab11a基因可能参与周围神经系统中TNTs结构的形成，而TNTs结构可能通过调节神经细胞通讯来影响周围神经再生。
