西亚试剂：Caprin-2 enhances canonical Wnt signaling through regulatin

The Journal of Cell Biology, Vol. 182, No. 5, 865-872 doi:10.1083/jcb.200803147

Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation

Yu Ding1, Ying Xi1, Ting Chen1, Ji-yong Wang1, Dong-lei Tao1, Zhi-Li Wu2, Yi-ping Li2, Chen Li3, Rong Zeng3, and Lin Li1

1 State Key Laboratory of Molecular Biology,
2 Laboratory of Molecular Cell Biology,
3 Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Correspondence to Lin Li: The low-density lipoprotein receptor–related proteins 5 and 6 (LRP5/6) are coreceptors for Frizzled and transmit signals from the plasma membrane to the cytosol. However, the mechanism for LRP5/6 signal transmission remains undefined. Here, we identify cytoplasmic activation/proliferation-associated protein 2 (Caprin-2) as a LRP5/6-binding protein. Our data show that Caprin-2 stabilizes cytosolic β-catenin and enhances lymphoid enhancer-binding factor 1/T cell factor–dependent reporter gene activity as well as the expression of Wnt target genes in mammalian cells.Morpholino-mediated knockdown of Caprin-2 in zebrafish embryos inhibits Wnt/β-catenin signaling and results in a dorsalized phenotype. Moreover,Caprin-2 facilitates LRP5/6 phosphorylation by glycogen synthase kinase 3, and thus enhances the interaction between Axin and LRP5/6. Therefore,Caprin-2 promotes activation of the canonical Wnt signaling pathway by regulating LRP5/6 phosphorylation.

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