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Published online September 1, 2008
doi:10.1083/jcb.200803147
The Journal of Cell Biology, Vol. 182, No. 5, 865-872
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Ding et al.
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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, and 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: lli{at}sibs.ac.cn

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.

Y. Ding and Y. Xi contributed equally to this paper.

Abbreviations used in this paper: Caprin, cytoplasmic activation/proliferation-associated protein; Dvl, Dishevelled; Fz, Frizzled; hpf, hours postfertilization; LEF, lymphoid enhancer-binding factor; LRP, low-density lipoprotein receptor–related protein; MO, morpholino oligonucleotides; TCF, T cell factor.

© 2008 Ding et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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