title: Rab8a/Rab11a regulate intercellular communications between neural cells via tunneling nanotubes.
abstract: 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.
authors.affiliation: 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.|Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Xue
authors.affiliation: Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Ju
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008055:Lipids / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016895:Culture Media, Serum-Free; D008055:Lipids; D009414:Nerve Growth Factors; D012313:RNA; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C530052:Rab8a protein, rat