Neural Responses to Taxation and Voluntary Giving Reveal Motives for Charitable Donations

to act downstream of LRP6 because dsh overexpression activates ß-catenin signaling inDrosophila LRP6 (arrow) mutants (23) and because the constitutively active Dfz2-Arrow fusion protein is inactive in dshmutants (24). The explanation for this discrepancy may be that overexpressing Dsh/Dvl leads to artificial sequestration of Axin or that the protein has multiple functions in the Wnt pathway. Taken together, the results suggest that Dvlmediated co-aggregation triggers LRP6 phosphorylation by CK1g. In this model (Fig. 4D), upon Wnt signaling Dvl aggregates form at the plasma membrane, where they co-cluster LRP6 with other pathway components including Fz, Axin, and GSK3b, in a “LRP6-signalosome.” The role of Wnt would be to bridge LRP6 and Fz (25, 5), which copolymerize on a Dvl platform. Clustering of LRP6 then provides a high local receptor concentration that triggers phosphorylation by CK1g and Axin recruitment. Predictions of this model are as follows: (i) artificial oligomerization of LRP6 should activate the receptor and (ii) oligomerized LRP6 should signal independent of Dvl. Indeed, forced oligomerization of LRP6 using a synthetic multimerizer is sufficient to induce Wnt signaling, and this oligomerization bypasses the need for Dvl (25). (iii) Constitutively active LRP6 should signal independently of Dvl because its self-aggregation should bypass the need for Dvl polymers. This is also the case as shown in reporter assays with Dvl siRNA knockdown (fig. S5, B and C), which supports previous findings (26, 25). (iv) If LRP6 aggregation is a prerequisite for phosphorylation by CK1g rather than its consequence, LRP6 aggregates should form even when the kinase is blocked. This is the case: Nonphosphorylated LRP6 aggregates were observed in response to Wnt treatment in cells transfected with dominantnegative CK1g (Fig. 4C). The model of LRP6signalosomes not only provides a mechanism for Wnt signal transduction but may also be relevant for the understanding of intracellular transport of maternal Wnt determinants in the fertilized Xenopus egg (27). References and Notes 1. P. Polakis, Genes Dev. 14, 1837 (2000). 2. R. T. Moon, B. Bowerman, M. Boutros, N. Perrimon, Science 296, 1644 (2002). 3. C. Y. Logan, R. Nusse, Annu. Rev. Cell Dev. Biol. 20, 781 (2004). 4. R. T. Moon, A. D. Kohn, G. V. De Ferrari, A. Kaykas, Nat. Rev. Genet. 5, 691 (2004). 5. X. He, M. Semenov, K. Tamai, X. Zeng, Development 131, 1663 (2004). 6. N. S. Tolwinski, E. Wieschaus, Trends Genet. 20, 177 (2004). 7. G. Davidson et al., Nature 438, 867 (2005). 8. X. Zeng et al., Nature 438, 873 (2005). 9. J. Klingensmith, R. Nusse, N. Perrimon, Genes Dev. 8, 118 (1994). 10. K. Itoh, B. K. Brott, G. U. Bae, M. J. Ratcliffe, S. Y. Sokol, J. Biol. 4, 3 (2005). 11. C. C. Malbon, H. Y. Wang, Curr. Top. Dev. Biol. 72, 153 (2006). 12. J. Mao et al., Mol. Cell 7, 801 (2001). 13. H. Yamamoto, H. Komekado, A. Kikuchi, Dev. Cell 11, 213 (2006). 14. J. D. Axelrod, J. R. Miller, J. M. Shulman, R. T. Moon, N. Perrimon, Genes Dev. 12, 2610 (1998). 15. U. Rothbächer et al., EMBO J. 19, 1010 (2000). 16. T. Schwarz-Romond et al., Nat. Struct. Mol. Biol. 14, 484 (2007). 17. D. G. Capelluto et al., Nature 419, 726 (2002). 18. J. T. Blitzer, R. Nusse, BMC Cell Biol. 7, 28 (2006). 19. S. Kishida et al., Mol. Cell. Biol. 19, 4414 (1999). 20. T. Schwarz-Romond, C. Merrifield, B. J. Nichols, M. Bienz, J. Cell Sci. 118, 5269 (2005). 21. M. J. Smalley et al., J. Cell Sci. 118, 5279 (2005). 22. A. Cliffe, F. Hamada, M. Bienz, Curr. Biol. 13, 960 (2003). 23. M. Wehrli et al., Nature 407, 527 (2000). 24. N. S. Tolwinski et al., Dev. Cell 4, 407 (2003). 25. F. Cong, L. Schweizer, H. Varmus, Development 131, 5103 (2004). 26. L. Li, J. Mao, L. Sun, W. Liu, D. Wu, J. Biol. Chem. 277, 5977 (2002). 27. C. Weaver, D. Kimelman, Development 131, 3491 (2004). 28. We thank R. Pepperkok for support in the EMBL Advanced Light Microscopy Facility; the Nikon Imaging Center at the University of Heidelberg and M. Boutros and D. Ingelfinger for help with siRNA experiments; A. Glinka for advice; N. Maltry for technical help; and J. Axelrod, A. Helenius, J. Nathans, R. Nusse, T. Schwarz-Romond, and M. Semenov for reagents. This work was supported by the European Union (Endotrack) and the Deutsche Forschungsgemeinschaft.