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O-GlcNAcylation of AMFR stabilizes TSPAN4 to regulate migrasome formation for viral release

文献类型：期刊论文

作者Yu, Linghui1,2; Li, Jiajia1,5; Han, Yiyang3; Yang, Xiao1,5; Fu, Yu1; Zhang, Weiyi1; Jiu, Yaming4; Cheng, Linling1,5; Ding, Binbin1,5
刊名NATURE COMMUNICATIONS
出版日期2026-01-07
卷号17期号:1页码:19
DOI10.1038/s41467-025-68220-3
通讯作者Cheng, Linling(linling@gird.cn) ; Ding, Binbin(dingbinbin1988@163.com)
英文摘要Migrasomes are migration-dependent organelles, serving as delivery packets to mediate release of cytoplasmic contents. Tetraspanin 4 (TSPAN4) acts as a marker for migrasomes and is essential for their formation. However, the regulatory mechanism(s) underlying TSPAN4-mediated migrasome biogenesis and its physiological functions remain to be elucidated. Here, we identified AMFR, an ER-resident E3 ligase, regulates migrasome formation through catalyzing the K48-linked polyubiquitination of TSPAN4 for degradation. Further, O-GlcNAcylation of AMFR by OGT at threonine 643 disrupts AMFR-TSPAN4 interactions, thereby stabilizing TSPAN4 and promoting migrasome formation. Additionally, viruses dynamically regulate migrasome formation by modulating AMFR O-GlcNAcylation and TSPAN4 ubiquitination. During the early stages of VSV or HSV-1 infection, viruses enhance migrasome formation and exploit these structures to spread among neighboring cells, whereas abolish migrasome formation during the late stages of infection. Our findings reveal a negatively regulatory mechanism governing migrasome biogenesis, and highlight how VSV and HSV-1 manipulate this process to facilitate their release.
WOS关键词AUTOCRINE MOTILITY FACTOR ; UBIQUITIN LIGASE ; FACTOR-RECEPTOR ; CELL-FUSION ; VIRUS ; ENTRY ; DEGRADATION ; MECHANISMS ; PROTEINS ; GP78
资助项目This work was supported by the National Natural Science Foundation of China (32422021, 32370809, U22A20337), the Research Fund of Guangzhou National Laboratory (GZNL2024A01008), and project GZNL2024B01005 supported by Guangzhou National Laboratory and Stat
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001686408800006
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/322854]  
专题中国科学院上海药物研究所
通讯作者Cheng, Linling; Ding, Binbin
作者单位1.Guangzhou Natl Lab, Guangzhou, Peoples R China
2.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Biochem & Mol Biol, Wuhan 430030, Peoples R China
3.CALTECH, Div Biol & Biol Engn, Pasadena, CA USA
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Linghui,Li, Jiajia,Han, Yiyang,et al. O-GlcNAcylation of AMFR stabilizes TSPAN4 to regulate migrasome formation for viral release[J]. NATURE COMMUNICATIONS,2026,17(1):19.
APA Yu, Linghui.,Li, Jiajia.,Han, Yiyang.,Yang, Xiao.,Fu, Yu.,...&Ding, Binbin.(2026).O-GlcNAcylation of AMFR stabilizes TSPAN4 to regulate migrasome formation for viral release.NATURE COMMUNICATIONS,17(1),19.
MLA Yu, Linghui,et al."O-GlcNAcylation of AMFR stabilizes TSPAN4 to regulate migrasome formation for viral release".NATURE COMMUNICATIONS 17.1(2026):19.

入库方式： OAI收割

来源：上海药物研究所

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