Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway

To understand how the Wnt coreceptor LRP-5 is involved in transducing the c anonical Wnt signals, we identified Axin as a protein that interacts with t he intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells , showed no effect on the canonical Wnt signaling pathway by itself, but ac ted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extrac ellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta -c atenin. Addition of Wnt caused the translocation of Axin to the membrane an d enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 s equences involved in interactions with Axin are required for LEF-1 activati on. Thus, we conclude that the binding of Axin to LRP-5 is an important par t of the Wnt signal transduction pathway.