LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation》.pdfVIP

Cellular Signalling 26 (2014) 1068–1074 Contents lists available at ScienceDirect Cellular Signalling journal homepage: /locate/cel lsi g LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation Jinxiao Chen b,1, Hongwei Yan b,1, Dan-ni Ren a,1, Yan Yin a,1, Zhi Li c, Qingqing He b, Da Wo b, Margaret Su-chun Ho b, Yihan Chen a,b, Zhongmin Liu a, Jianhua Yang b, Shangfeng Liu d,⁎⁎, Weidong Zhu a,b,⁎ a Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Shanghai, China b Tongji University School of Medicine, Shanghai, China c Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan d Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, China a r t i c l e i n f o a b s t r a c t Article history: Canonical Wnt/β-catenin signaling pathway plays important roles in multiple aspects of cellular responses in de- Received 17 December 2013 velopment and diseases. It is currently thought that Wnt receptor Frizzled (Frz) exists separately to Wnt Accepted 29 December 2013 coreceptors LRP5 and LRP6 (LRP5/6), and that Wnt–Frz–LRP5/6 triple complex formation bridged by Wnt ligand Available online 8 January 2014 is needed for canonical pathway activation. We recently showed that Frz and LRP5/6 interact with each other in the absence of Wnt ligand binding and this interaction maintains the Frz–LRP5/6 c