| First Author | Sun S | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 8377 |
| PubMed ID | 39333081 | Mgi Jnum | J:359350 |
| Mgi Id | MGI:7738024 | Doi | 10.1038/s41467-024-52729-0 |
| Citation | Sun S, et al. (2024) Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed alpha-tubulin lactylation. Nat Commun 15(1):8377 |
| abstractText | Posttranslational modifications (PTMs) of tubulin, termed the "tubulin code", play important roles in regulating microtubule functions within subcellular compartments for specialized cellular activities. While numerous tubulin PTMs have been identified, a comprehensive understanding of the complete repertoire is still underway. In this study, we report that alpha-tubulin lactylation is catalyzed by HDAC6 by using lactate to increase microtubule dynamics in neurons. We identify lactylation on lysine 40 of alpha-tubulin in the soluble tubulin dimers. Notably, lactylated alpha-tubulin enhances microtubule dynamics and facilitates neurite outgrowth and branching in cultured hippocampal neurons. Moreover, we discover an unexpected function of HDAC6, acting as the primary lactyltransferase to catalyze alpha-tubulin lactylation. HDAC6-catalyzed lactylation is a reversible process, dependent on lactate concentrations. Intracellular lactate concentration triggers HDAC6 to lactylate alpha-tubulin, a process dependent on its deacetylase activity. Additionally, the lactyltransferase activity may be conserved in HDAC family proteins. Our study reveals the primary role of HDAC6 in regulating alpha-tubulin lactylation, establishing a link between cell metabolism and cytoskeleton functions. |
