ZFIN ID: ZDB-PUB-080908-2
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
Ding, Y., Xi, Y., Chen, T., Wang, J.Y., Tao, D.L., Wu, Z.L., Li, Y.P., Li, C., Zeng, R., and Li, L.
Date: 2008
Source: The Journal of cell biology   182(5): 865-872 (Journal)
Registered Authors: Li, Lin
Keywords: none
MeSH Terms:
  • Animals
  • Axin Protein
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/physiology*
  • Cell Line
  • Cytoplasm/metabolism
  • Embryo, Nonmammalian/anatomy & histology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation
  • Gene Silencing
  • Glycogen Synthase Kinase 3/metabolism
  • Humans
  • LDL-Receptor Related Proteins/metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lymphoid Enhancer-Binding Factor 1/genetics
  • Lymphoid Enhancer-Binding Factor 1/metabolism
  • Phenotype
  • Phosphorylation
  • Repressor Proteins/metabolism
  • Signal Transduction*
  • TCF Transcription Factors/genetics
  • TCF Transcription Factors/metabolism
  • Transcription, Genetic
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • beta Catenin/metabolism
PubMed: 18762581 Full text @ J. Cell Biol.
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.