The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis

NWIPB OpenIR

	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
	2021
发表期刊	SCIENCE CHINA-LIFE SCIENCES
卷号	64 期号:11
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	ER membrane protein complex Emc3 angiogenesis cell proliferation lithium chloride Wnt
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/60790
专题	中国科学院西北高原生物研究所
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]. SCIENCE CHINA-LIFE SCIENCES,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).