title: Sorting nexin 27 interacts with Fzd7 and mediates Wnt signalling.
abstract: SNX27 is the only sorting nexin (SNX) that contains a PDZ domain, which interacts with PDZ-binding motif of target proteins to regulate the trafficking of these proteins. We here showed that SNX27 interacts with Frizzled (Fzd) receptors via PDZ domain interaction. Immunofluorescence microscopy revealed that Fzd7 can be internalized and associate with SNX27-containing endosomal membrane. In addition, SNX27 enhances the endocytosis of Fzd7 and promotes the degradation of Fzd7. Further examination demonstrated that SNX27 inhibits the Wnt regulated transcription activity of TCF/LEF. Our results suggested that SNX27 interacts with Frizzled receptors to regulate the endocytosis and stability of Fzds, and consequently mediates canonical Wnt signalling.
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Xiuyong
authors.initials: X
authors.lastname: Hu
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Wanming
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China zhangzhiming164@aliyun.com xmuibrwtl@xmu.edu.cn.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, Fujian, China zhangzhiming164@aliyun.com xmuibrwtl@xmu.edu.cn.
authors.forename: Tuanlao
authors.initials: T
authors.lastname: Wang
mesh_terms: D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D061986:MCF-7 Cells; D021381:Protein Transport / Q000502:physiology; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C115810:FZD7 protein, human; D051157:Frizzled Receptors; C522885:SNX27 protein, human; D058305:Sorting Nexins
keywords: Fzd7; PDZ domain; SNX27; Wnt signalling