alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation

doi:10.1038/s41467-021-24376-2

	alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
	Xie, Xuan 1,2; Wang, Shaogang1,2,3 ; Li, Mingyi 1,2; Diao, Lei 1; Pan, Xingyu 4; Chen, Jijun 4; Zou, Weiguo 1,2; Zhang, Xu2,3,4,5 ; Feng, Wenfeng 1,4; Bao, Lan1,2,3
	2021-07-05
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-24376-2
摘要	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. Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, alpha -TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000672713100002
出版者	NATURE RESEARCH
原始文献类型	Article
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/127725
专题	生命科学与技术学院_特聘教授组_张旭组生命科学与技术学院_特聘教授组_鲍岚组生命科学与技术学院_博士生
通讯作者	Feng, Wenfeng; Bao, Lan
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Shanghai Res Ctr Brain Sci & Brain Inspired Intel, Shanghai, Peoples R China; 5.Chinese Acad Sci, Lab Percept Network, Shanghai Adv Res Inst, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Xie, Xuan,Wang, Shaogang,Li, Mingyi,et al. alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Xie, Xuan.,Wang, Shaogang.,Li, Mingyi.,Diao, Lei.,Pan, Xingyu.,...&Bao, Lan.(2021).alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation.NATURE COMMUNICATIONS,12(1).
MLA	Xie, Xuan,et al."alpha-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation".NATURE COMMUNICATIONS 12.1(2021).