Deubiquitinase USP9X controls Wnt signaling for CNS vascular formation and barrier maintenance

IF 10.7 1区 生物学 Q1 CELL BIOLOGY Developmental cell Pub Date : 2025-02-04 DOI:10.1016/j.devcel.2025.01.009
Yi Lei, Jiandong Hu, Jiyun Zhao, Qiangyun Liu, Selena Wei Zhang, Fangfang Wu, Yuming Liu, Honglei Ren, Xiaoyang Qin, Xudong Wu, Fei Gao, Junhao Hu, Kunfu Ouyang, Qiang Liu, Xiangjian Zheng, Lei Shi, Xiaohong Wang
{"title":"Deubiquitinase USP9X controls Wnt signaling for CNS vascular formation and barrier maintenance","authors":"Yi Lei, Jiandong Hu, Jiyun Zhao, Qiangyun Liu, Selena Wei Zhang, Fangfang Wu, Yuming Liu, Honglei Ren, Xiaoyang Qin, Xudong Wu, Fei Gao, Junhao Hu, Kunfu Ouyang, Qiang Liu, Xiangjian Zheng, Lei Shi, Xiaohong Wang","doi":"10.1016/j.devcel.2025.01.009","DOIUrl":null,"url":null,"abstract":"Deubiquitinating enzymes play crucial roles in various cellular activities, yet their involvement in central nervous system (CNS) vascularization and barrier function remains elusive. Canonical Wnt signaling is essential for proper CNS vascularization and barrier maintenance. Using a loss-of-function screening for Wnt-signaling activity, we identified ubiquitin-specific peptidase 9 X-linked (USP9X) as a key regulator in brain endothelial cells (BECs). Endothelium-specific <em>Usp9x</em> knockout mice exhibit reduced Wnt-signaling activity, compromising CNS vascularization and barrier function during development. Activation of Wnt signaling rescues these defects. Mechanistically, we identified β-catenin as a direct substrate of USP9X, with USP9X catalyzing K48 polyubiquitin chains to stabilize β-catenin. In pathological mouse models of impaired CNS vascular barrier function, including intracerebral hemorrhage and an oxygen-induced retinopathy, loss of <em>Usp9x</em> intensifies barrier disruption, accentuating defects. This finding implicates USP9X as a critical regulator of CNS vascularization and barrier function through Wnt signaling, offering insights into CNS disease implications.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"122 1","pages":""},"PeriodicalIF":10.7000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.devcel.2025.01.009","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Deubiquitinating enzymes play crucial roles in various cellular activities, yet their involvement in central nervous system (CNS) vascularization and barrier function remains elusive. Canonical Wnt signaling is essential for proper CNS vascularization and barrier maintenance. Using a loss-of-function screening for Wnt-signaling activity, we identified ubiquitin-specific peptidase 9 X-linked (USP9X) as a key regulator in brain endothelial cells (BECs). Endothelium-specific Usp9x knockout mice exhibit reduced Wnt-signaling activity, compromising CNS vascularization and barrier function during development. Activation of Wnt signaling rescues these defects. Mechanistically, we identified β-catenin as a direct substrate of USP9X, with USP9X catalyzing K48 polyubiquitin chains to stabilize β-catenin. In pathological mouse models of impaired CNS vascular barrier function, including intracerebral hemorrhage and an oxygen-induced retinopathy, loss of Usp9x intensifies barrier disruption, accentuating defects. This finding implicates USP9X as a critical regulator of CNS vascularization and barrier function through Wnt signaling, offering insights into CNS disease implications.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
求助全文
约1分钟内获得全文 去求助
文献相关原料
公司名称
产品信息
索莱宝
Urea
来源期刊
Developmental cell
Developmental cell 生物-发育生物学
CiteScore
18.90
自引率
1.70%
发文量
203
审稿时长
3-6 weeks
期刊介绍: Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.
期刊最新文献
Pancreatic alpha and beta cell fate choice is directed by apical-basal polarity dynamics snRNA-seq analysis of the moss Physcomitrium patens identifies a conserved cytokinin-ESR module promoting pluripotent stem cell identity Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice Florigen-producing cells express FPF1-LIKE PROTEIN 1 to accelerate flowering and stem growth in Arabidopsis Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1