Glycogen synthase kinase 3 drives thymocyte egress by suppressing β-catenin activation of Akt

Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell–specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, β-catenin accumulated in the cy...

Full description

Saved in:

Bibliographic Details
Published in:	Science advances Vol. 7; no. 41; p. eabg6262
Main Authors:	Liu, Chenfeng, Ma, Lei, Wang, Yuxuan, Zhao, Jiayi, Chen, Pengda, Chen, Xian, Wang, Yingxin, Hu, Yanyan, Liu, Yun, Jia, Xian, Yang, Zhanghua, Yin, Xingzhi, Wu, Jianfeng, Wu, Suqin, Zheng, Haiping, Ma, Xiaohong, Sun, Xiufeng, He, Ying, Lin, Lianghua, Fu, Yubing, Liao, Kunyu, Zhou, Xiaojuan, Jiang, Shan, Fu, Guofeng, Tang, Jian, Han, Wei, Chen, Xiao Lei, Fan, Wenzhu, Hong, Yazhen, Han, Jiahuai, Huang, Xiangyang, Li, Bo-An, Xiao, Nengming, Xiao, Changchun, Fu, Guo, Liu, Wen-Hsien
Format:	Journal Article
Language:	English
Published:	United States American Association for the Advancement of Science 08-10-2021
Subjects:	Biomedicine and Life Sciences Cell Biology Immunology SciAdv r-articles
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell–specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, β-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P expression, thereby preventing emigration of thymocytes. A cytoplasmic membrane-localized β-catenin excluded from the nucleus promoted Akt activation, suggesting a new function of β-catenin independent of its role as a transcriptional activator. Furthermore, genetic ablation of β-catenin, retroviral expression of a dominant negative Akt mutant, and transgenic expression of a constitutively active Foxo1 restored emigration of GSK3-deficient thymocytes. Our findings establish an essential role for GSK3 in thymocyte egress and reveal a previously unidentified signaling function of β-catenin in the cytoplasm.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. Lead contact. Present address: State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, China.
ISSN:	2375-2548 2375-2548
DOI:	10.1126/sciadv.abg6262