Erbin is required for myelination in regenerated axons after injury.
Erbin is required for myelination in regenerated axons after injury.
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损伤后再生轴突的髓鞘形成需要 Erbin
DOI：
10.1523/jneurosci.2466-12.2012
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发表时间：
2012-10-24
期刊：
影响因子：
--
通讯作者：
Mei L
中科院分区：
文献类型：
--
作者：
Liang C;Tao Y;Shen C;Tan Z;Xiong WC;Mei L
神经调节蛋白1（NRG 1）是轴突衍生因子，其以依赖于跨膜酪氨酸激酶ErbB 2和ErbB 3的方式对雪旺细胞（SC）发育和髓鞘形成至关重要。最近的研究表明，NRG 1信号在损伤后再生神经的髓鞘再生中起作用。在这项研究中，我们研究了Erbin的作用，ErbB 2蛋白相互作用损伤神经的髓鞘再生。我们发现，Erbin的表达显着增加，在受伤的神经。在神经损伤后功能恢复受损的erbin−/−小鼠中，有髓轴突较少，有髓轴突的g-比率增加。这些结果表明Erbin在再生轴突髓鞘形成中的必要作用。Erbin消融对BrdU标记和TUNEL标记的SC数量几乎没有影响，这表明其机制独立于增殖或凋亡的改变。我们证明了Erbin突变小鼠在提高或维持ErbB 2水平和在轴突中产生NRG 1方面受损。总之，这些观察结果表明，Erbin是损伤后再生轴突髓鞘再生所必需的，可能是通过调节ErbB 2和NRG 1水平，确定了一种调节髓鞘再生的新参与者。
Neuregulin 1 (NRG1) is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ErbB2 and ErbB3. Recent studies suggest that NRG1 signaling plays a role in remyelination of regenerated nerves after injury. In this study, we investigated the role of Erbin, a protein that interacts with ErbB2 in remyelination of injured nerves. We show that Erbin expression increased dramatically in injured nerves. Myelinated axons were fewer, and g-ratios of those that were myelinated were increased in erbin−/− mice, which were impaired in functional recovery from nerve injury. These results indicate a necessary role of Erbin in remyelination of regenerating axons. Erbin ablation had little effect on numbers of BrdU-labeled and TUNEL-labeled SCs, suggesting mechanisms independent of altered proliferation or apoptosis. We demonstrated that Erbin mutant mice were impaired in raising or maintaining the levels of ErbB2 and in producing NRG1 in axons. Together, these observations demonstrate that Erbin is required for remyelination of regenerated axons after injury, probably by regulating ErbB2 and NRG1 levels, identifying a novel player in regulating remyelination.