Sorting nexin 27 interacts with Fzd7 and mediates Wnt signalling.
Sorting nexin 27 interacts with Fzd7 and mediates Wnt signalling.
复制标题
分选 nexin 27 与 Fzd7 相互作用并介导 Wnt 信号传导。
DOI：
10.1042/bsr20150205
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发表时间：
2016-01-07
影响因子：
4
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Sun L;Hu X;Chen W;He W;Zhang Z;Wang T
本工作发现，SNX27与Frizzled型受体(FZD)通过PDZ结构域相互作用，是SNX27的新的相互作用伙伴。对SNX27与FZD7相互作用的功能研究表明，SNX27促进FZD7的降解，从而下调Wnt信号。SNX27是唯一一个含有PDZ结构域的分类连接素(SNX)，它与靶蛋白的PDZ结合基序相互作用，调节这些蛋白的运输。我们发现SNX27通过PDZ结构域与FrizzledFZD受体相互作用。免疫荧光显微镜显示FZD7可内化并与含SNX27的内膜结合。此外，SNX27还能增强FZD7的内吞作用，促进FZD7的降解。进一步的检测表明SNX27抑制了Wnt调控的TCF/Lef的转录活性。我们的结果表明，SNX27与FrizzledR相互作用，调节Fzds的内吞作用和稳定性，从而介导典型的Wnt信号。
This work found that sorting nexin 27 (SNX27) interacts with Frizzled receptors (Fzds) through PDZ domain interaction, which act as novel interacting partners for SNX27. Functional investigation of the interaction of SNX27 with Fzd7 revealed that SNX27 promotes the degradation of Fzd7, thus down-regulating Wnt signalling. 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.