Eml1通过增强αTAT1介导的微管乙酰化促进轴突生长。

IF 4.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-06-17 DOI:10.1016/j.bbamcr.2024.119770
Yufang Zhang , Tuchen Guan , Zhen Li , Beibei Guo , Xiaoqian Luo , Longyu Guo , Mingxuan Li , Man Xu , Mei Liu , Yan Liu
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摘要

微管的稳定对轴突的生长和再生至关重要,许多微管相关蛋白都参与了这一过程。在这项研究中,我们发现敲除棘皮动物微管相关蛋白样1(EML1)会阻碍培养的皮层神经元和背根神经节神经元的轴突生长。我们进一步发现,EML1促进了微管的乙酰化,而抑制EML1导致的轴突生长障碍可以通过去乙酰化酶抑制剂的处理得到恢复,这表明EML1影响了微管蛋白的乙酰化。此外,我们还验证了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。因此我们推测,EML1可能通过α-微管蛋白乙酰转移酶1调控微管乙酰化和稳定,进而促进轴突生长。最后,我们验证了在体内敲除EML1也会抑制坐骨神经再生。我们的研究结果揭示了EML1在轴突再生过程中对微管乙酰化的新作用。
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Eml1 promotes axonal growth by enhancing αTAT1-mediated microtubule acetylation

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.

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来源期刊
CiteScore
10.00
自引率
2.00%
发文量
151
审稿时长
44 days
期刊介绍: BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.
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