中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (6): 1816-1824.doi: 10.4103/NRR.NRR-D-23-00529

• 原著:神经损伤修复保护与再生 • 上一篇    

Rab5蛋白促进斑马鱼毛特纳神经元轴突再生和功能恢复的作用机制

  

  • 出版日期:2025-06-15 发布日期:2024-11-12

Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons

Jiantao Cui# , Yueru Shen# , Zheng Song, Dinggang Fan, Bing Hu*   

  1. Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China
  • Online:2025-06-15 Published:2024-11-12
  • Contact: Bing Hu, PhD, bhu@ustc.edu.cn.
  • Supported by:
    This study was supported by the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM, No. QYZD20220002; the National Natural Science Foundation of China, No. 82071357; and a grant from the Ministry of Science and Technology of China, No. 2019YFA0405600 (all to BH).

摘要:

Rab5蛋白是一种可参与细胞内膜转运的小GTP酶蛋白,其功能是与多种效应蛋白结合并调节细胞反应,如运输小泡形成及其与细胞膜的融合。据报道,Rab5蛋白在斑马鱼胚胎的发育中起着重要的作用;然而,Rab5蛋白在中枢神经系统轴突再生中的作用尚不清楚。作者通过独创的单细胞电转染技术结合双光子毁损轴突构建出斑马鱼幼鱼毛特纳神经元轴突损伤-再生模型。结果发现,毛特纳神经元内过表达Rab5可显著促进其轴突的再生,并增加神经元轴突内部囊泡数量;而Rab5蛋白抑制剂CID-1067700则会使得轴突再生能力减弱。同时发现,Rab5蛋白在毛特纳神经元轴突修复过程中会激活PI3K,并促进斑马鱼运动功能的恢复,且PI3K下游分子mTOR的抑制剂雷帕霉素会阻碍轴突再生。因此表明,Rab5蛋白可通过激活PI3K信号通路促进轴突损伤后的再生及功能恢复。

https://orcid.org/0009-0003-9148-1005 (Jiantao Cui); https://orcid.org/0000-0001-7670-6243 (Yueru Shen); 

https://orcid.org/0009-0007-8309-8398 (Zheng Song); 
https://orcid.org/0009-0009-7234-5618 (Dinggang Fan); https://orcid.org/0000-0001-8627-5272 (Bing Hu)

关键词: Rab5蛋白, 斑马鱼, 毛特纳神经元, 轴突再生, 神经再生

Abstract: Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo; however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700 markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase (PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

Key words: axonal regeneration, Mauthner cell, nerve regeneration, Rab5, zebrafish