气候变化领域集成服务门户(CCPortal): The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis

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DOI	10.1007/s11427-021-1941-7
	The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis
	Yang, Mu; Li, Shujin; Liu, Wenjing; Li, Xiao; He, Yunqi; Yang, Yeming; Sun, Kuanxiang; Zhang, Lin; Tian, Wanli; Duan, Lixin; Chen, Huafu; Yao, Dezhong; Yang, Zhenglin; Zhu, Xianjun
通讯作者	Yang, ZL ; Zhu, XJ (通讯作者)，Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Med Genet, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Peoples R China. ; Yang, ZL ; Zhu, XJ (通讯作者)，Chinese Acad Med Sci 2019RU026, Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Res Unit Blindness Prevent, Chengdu 610072, Peoples R China. ; Zhu, XJ (通讯作者)，Chinese Acad Sci, Key Lab Tibetan Med Res, Xining 810008, Peoples R China. ; Zhu, XJ (通讯作者)，Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Peoples R China. ; Zhu, XJ (通讯作者)，Shangqiu First Peoples Hosp, Dept Ophthalmol, Shangqiu 476000, Peoples R China. ; Yang, ZL ; Zhu, XJ (通讯作者)，Chinese Acad Sci, Sichuan Translat Med Hosp, Nat Prod Res Ctr, Inst Chengdu Biol, Chengdu 610072, Peoples R China.
发表日期	2021
ISSN	1674-7305
EISSN	1869-1889
起始页码	1868
结束页码	1883
卷号	64 期号:11
英文摘要	The endoplasmic reticulum (ER) membrane protein complex (EMC) regulates the synthesis and quality control of membrane proteins with multiple transmembrane domains. One of the membrane spanning subunits, EMC3, is a core member of the EMC complex that provides essential hydrophilic vestibule for substrate insertion. Here, we show that the EMC subunit Emc3 plays critical roles in the retinal vascular angiogenesis by regulating Norrin/Wnt signaling. Postnatal endothelial cell (EC)-specific deletion of Emc3 led to retarded retinal vascular development with a hyperpruned vascular network, the appearance of blunt-ended, aneurysm-like tip endothelial cells (ECs) with reduced numbers of filopodia and leakage of erythrocytes at the vascular front. Diminished tube formation and cell proliferation were also observed in EMC3 depleted human retinal endothelial cells (HRECs). We then discovered a critical role for EMC3 in expression of FZD4 receptor of beta-catenin signaling using RNA sequencing, real-time quantitative PCR (RT-qPCR) and luciferase reporter assay. Moreover, augmentation of Wnt activity via lithium chloride (LiCl) treatment remarkably enhanced beta-catenin signaling and cell proliferation of HRECs. Additionally, LiCl partially reversed the angiogenesis defects in Emc3-cKO mice. Our data reveal that Emc3 plays essential roles in angiogenesis through direct control of FZD4 expression and Norrin/beta-catenin signaling.
关键词	RETINAL VASCULAR DEVELOPMENT BETA-CATENIN ZIKA VIRUS WNT NORRIN VARIANT IDENTIFICATION FRIZZLED-4 RECEPTORS TSPAN12
英文关键词	ER membrane protein complex; Emc3; angiogenesis; cell proliferation; lithium chloride; Wnt
语种	英语
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS类目	Biology
WOS记录号	WOS:000661416800002
来源期刊	SCIENCE CHINA-LIFE SCIENCES
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/254810
作者单位	[Yang, Mu; Li, Shujin; Liu, Wenjing; Li, Xiao; He, Yunqi; Yang, Yeming; Sun, Kuanxiang; Zhang, Lin; Tian, Wanli; Duan, Lixin; Yang, Zhenglin; Zhu, Xianjun] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Med Genet, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Peoples R China; [Yang, Mu; Li, Shujin; Yang, Zhenglin; Zhu, Xianjun] Chinese Acad Med Sci 2019RU026, Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Res Unit Blindness Prevent, Chengdu 610072, Peoples R China; [Zhu, Xianjun] Chinese Acad Sci, Key Lab Tibetan Med Res, Xining 810008, Peoples R China; [Zhu, Xianjun] Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Peoples R China; [Zhu, Xianjun] Shangqiu First Peoples Hosp, Dept Ophthalmol, Shangqiu 476000, Peoples R China; [He, Yunqi; Yang, Zhenglin; Zhu, Xianjun] Chinese Acad Sci, Sichuan Translat Med Hosp, Nat Prod Res Ctr, Inst Chengdu Biol, Chengdu 610072, Peoples R China; [Chen, Huafu; Yao, Dezhong] Univ Elect Sci & Technol China, C...
推荐引用方式 GB/T 7714	Yang, Mu,Li, Shujin,Liu, Wenjing,et al. The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis[J]. 中国科学院西北生态环境资源研究院,2021,64(11).
APA	Yang, Mu.,Li, Shujin.,Liu, Wenjing.,Li, Xiao.,He, Yunqi.,...&Zhu, Xianjun.(2021).The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis.SCIENCE CHINA-LIFE SCIENCES,64(11).
MLA	Yang, Mu,et al."The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis".SCIENCE CHINA-LIFE SCIENCES 64.11(2021).