Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed Î±-tubulin lactylation

doi:10.1038/s41467-024-52729-0

	Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed Î±-tubulin lactylation
	Shuangshuang Sun; Zhe Xu; Liying He; Yihui Shen; Yuqing Yan; Xubing Lv; Xujing Zhu; Wei Li; Wei-Ya Tian; Yongjun Zheng; Sen Lin; Yadong Sun; Lei Li
	2024-09-27
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	15 期号:1
DOI	10.1038/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 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.
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收录类别	SCI
语种	英语
资助项目	CAS Center for Excellence in Molecular Cell Science["91949117","31871044"] ; National Natural Science Foundation of China[LG-GG-202401-ADA060200]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001377360500009
出版者	NATURE PORTFOLIO
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/433546
专题	生命科学与技术学院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_博士生
共同第一作者	Zhe Xu
通讯作者	Lei Li
作者单位	ShanghaiTech University, School of Life Science and Technology
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
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 Î±-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 Î±-tubulin lactylation.NATURE COMMUNICATIONS,15(1).
MLA	Shuangshuang Sun,et al."Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed Î±-tubulin lactylation".NATURE COMMUNICATIONS 15.1(2024).