Antagonizing Wnt at the Cell Surface

Wnts are secreted glycoproteins that regulate embryonic development through Frizzled (Fz) cell-surface receptors. Subsequent regulation of gene expression occurs through relocalization of intracellular β-catenin to the nucleus. The mechanism by which another extracellular molecule called Dickkopf (DKK) blocks Wnt signaling is now described by Mao et al. DKK binds to LDL-receptor-related protein 6 (LRP6), a transmembrane protein that also regulates β-catenin. DKK binds to a region of LRP6 that is not involved in LRP6's interaction with the Wnt-Fz complex, and the DKK-LRP6 association did not affect Wnt-Fz interaction. The authors used Xenopus embryos to show that LRP6 promotes Wnt-induced posterior development. However, in the presence of DKK, this developmental process is inhibited, resulting in anterior embryonic development instead. R. Nusse offers insights into the signaling link between LRP6 and Fz. B. Mao, W. Wu, Y. Li, D. Hoppe, P. Stannek, A. Glinka, C. Niehrs, LDL-receptor-related protein 6 is a receptor for Dickkopf proteins, Nature 411 , 321-325 (2001). [Online Journal] R. Nusse, Making head or tail of Dickkop, Nature 411 : 255-256 (2001). [Online Journal]