title: Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.
abstract: 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 beta-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/beta-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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Ying
authors.initials: Y
authors.lastname: Xi
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Ji-yong
authors.initials: JY
authors.lastname: Wang
authors.forename: Dong-lei
authors.initials: DL
authors.lastname: Tao
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Wu
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Lin
authors.initials: L
authors.lastname: Li