Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation
2024-09-27
发表期刊NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN2041-1723
EISSN2041-1723
卷号15期号:1
发表状态已发表
DOI10.1038/s41467-024-52729-0
摘要

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 α-tubulin lactylation is catalyzed by HDAC6 by using lactate to increase microtubule dynamics in neurons. We identify lactylation on lysine 40 of α-tubulin in the soluble tubulin dimers. Notably, lactylated α-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 α-tubulin lactylation. HDAC6-catalyzed lactylation is a reversible process, dependent on lactate concentrations. Intracellular lactate concentration triggers HDAC6 to lactylate α-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 α-tubulin lactylation, establishing a link between cell metabolism and cytoskeleton functions.

关键词Microtubule PTMs Lactylation HDAC6 Microtubule dynamic instabilit
学科门类理学 ; 理学::生物学
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收录类别SCI
语种英语
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被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/527166
专题生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_李磊组
生命科学与技术学院_硕士生
生命科学与技术学院_PI研究组_孙亚东组
共同第一作者Zhe Xu
通讯作者Yadong Sun
作者单位
1.ShanghaiTech University
2.Fudan Univ, Huadong Hosp, Dept Pain Management, Shanghai, Peoples R China
3.Shanghai Clin Res & Trial Ctr, Shanghai, Peoples R China
4.Army Medical University
第一作者单位上海科技大学
通讯作者单位上海科技大学
第一作者的第一单位上海科技大学
推荐引用方式
GB/T 7714
Shuangshuang Sun,Zhe Xu,Liying He,et al. Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation[J]. NATURE COMMUNICATIONS,2024,15(1).
APA Shuangshuang Sun.,Zhe Xu.,Liying He.,Yihui Shen.,Yuqing Yan.,...&Lei Li.(2024).Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation.NATURE COMMUNICATIONS,15(1).
MLA Shuangshuang Sun,et al."Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation".NATURE COMMUNICATIONS 15.1(2024).
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