Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Medical School, Nantong University, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, China.
Biochim Biophys Acta Mol Cell Res. 2024 Oct;1871(7):119770. doi: 10.1016/j.bbamcr.2024.119770. Epub 2024 Jun 17.
Microtubule stabilization is critical for axonal growth and regeneration, and many microtubule-associated proteins are involved in this process. In this study, we found that the knockdown of echinoderm microtubule-associated protein-like 1 (EML1) hindered axonal growth in cultured cortical and dorsal root ganglion neurons. We further revealed that EML1 facilitated the acetylation of microtubules and that the impairment of axonal growth due to EML1 inhibition could be restored by treatment with deacetylase inhibitors, suggesting that EML1 affected tubulin acetylation. Moreover, we verified an interaction between EML1 and the alpha-tubulin acetyltransferase 1, which is responsible for the acetylation of alpha-tubulin. We thus proposed that EML1 might regulate microtubule acetylation and stabilization via alpha-tubulin acetyltransferase 1 and then promote axon growth. Finally, we verified that the knockdown of EML1 in vivo also inhibited sciatic nerve regeneration. Our findings revealed a novel effect of EML1 on microtubule acetylation during axonal regeneration.
微管稳定对于轴突生长和再生至关重要,许多微管相关蛋白参与了这个过程。在这项研究中,我们发现棘皮动物微管相关蛋白样 1 (EML1) 的敲低会阻碍培养的皮质和背根神经节神经元的轴突生长。我们进一步揭示,EML1 促进微管乙酰化,并且通过用去乙酰化酶抑制剂处理可以恢复由于 EML1 抑制引起的轴突生长受损,这表明 EML1 影响微管蛋白乙酰化。此外,我们验证了 EML1 与负责α-微管蛋白乙酰化的α-微管蛋白乙酰转移酶 1 之间的相互作用。因此,我们提出 EML1 可能通过α-微管蛋白乙酰转移酶 1 来调节微管乙酰化和稳定,从而促进轴突生长。最后,我们验证了体内敲低 EML1 也会抑制坐骨神经再生。我们的发现揭示了 EML1 在轴突再生过程中对微管乙酰化的新作用。