| First Author | Xie X | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 4113 |
| PubMed ID | 34226540 | Mgi Jnum | J:307957 |
| Mgi Id | MGI:6725615 | Doi | 10.1038/s41467-021-24376-2 |
| Citation | Xie X, et al. (2021) alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. Nat Commun 12(1):4113 |
| abstractText | Tri-methylation on lysine 40 of alpha-tubulin (alpha-TubK40me3) is a recently identified post-translational modification involved in mitosis and cytokinesis. However, knowledge about alpha-TubK40me3 in microtubule function and post-mitotic cells remains largely incomplete. Here, we report that alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. alpha-TubK40me3 is enriched in mouse cerebral cortex during embryonic day (E)14 to E16. Knockdown of alpha-tubulin methyltransferase SETD2 at E14 leads to the defects in neuronal migration, which could be restored by overexpressing either a cytoplasm-localized SETD2 truncation or alpha-TubK40me3-mimicking mutant. Furthermore, alpha-TubK40me3 is preferably distributed on polymerized microtubules and potently promotes tubulin nucleation. Downregulation of alpha-TubK40me3 results in reduced microtubule abundance in neurites and disrupts neuronal polarization, which could be rescued by Taxol. Additionally, alpha-TubK40me3 is increased after losing alpha-tubulin K40 acetylation (alpha-TubK40ac) and largely rescues alpha-TubK40ac function. This study reveals a critical role of alpha-TubK40me3 in microtubule formation and neuronal development. |
