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inner nuclear membrane protein TMEM201 maintains endothelial cell migration and angiogenesis by interacting with the LINC complex

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Journal of Molecular Cell Biology 2022年第3期14卷 48-60页

作者： Yutian Zhang Ya Kong Haoran Guo Yun Liu Yi Zang Jia Li University of Chinese Academy of Sciences Beĳing 100049China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug ScreeningChina Pharmaceutical UniversityNanjing 210009China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Open Studio for Druggability Research of Marine Natural Products Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China

The nuclear envelope comprises the outer nuclear membrane,inner nuclear membrane(INM),and ***∼60 INM proteins have been identified,only a few of them have been well characterized,revealing their crucial *** group focused on the INM protein transmembrane protein 201(TMEM201),whose role in cellular function remains to be *** this study,we investigated the role of TMEM201 in endothelial cell migration and *** of TMEM201 expression by short hairpin RNA-mediated interference impeded human umbilical vein endothelial cell(HUVEC)angiogenic behavior in tube formation and fibrin gel bead sprouting ***,TMEM201-deficient HUVECs exhibited impaired migration *** next explored the underlying mechanism and found that the N-terminal of TMEM201 interacted with the linker of nucleoskeleton and cytoskeleton complex and was required for regulating endothelial cell migration and *** in vitro findings were further confirmed by using in vivo *** Tmem201-knockout mice,retinal vessel development was arrested and aortic ring sprouting was *** addition,loss of tmem201 impaired zebrafish intersegmental vessel *** summary,TMEM201 was shown to regulate endothelial cell migration and control the process of *** study is the first to reveal the role of INM proteins in the vascular system and angiogenesis.

关键词： transmembrane protein 201 inner nuclear membrane LINC complex endothelial cell migration angiogenesis

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