The Wnt genes encode a large family of secreted proteins that play a key role in embryonic development and tissue differentiation in many species (Rijsewijk et al., 1987; Nusse and Varmus, 1992). Genetic and biochemical studies have suggested that the frizzled proteins are cell surface receptors for Wnts (Vinson et al., 1989; Chan et al. , 1992; Bhanot et al., 1996; Wang et al., 1996). In paral...

Signaling molecules of the Wnt gene family are involved in the regulation of dorso-ventral, segmental and tissue polarity in Xenopus and Drosophila embryos. Members of the frizzled gene family, such as Drosophila frizzled-2 and rat frizzled-1, have been shown encode Wnt binding activity and to engage intracellular signal transduction molecules known to be part of the Wnt signaling pathway. Here...

Approximately 1 million people in the United States suffer from interstitial cystitis, a chronic painful urinary bladder disorder characterized by thinning or ulceration of the bladder epithelial lining; its etiology is unknown. We have identified a glycosylated frizzled-related peptide inhibitor of cell proliferation that is secreted specifically by bladder epithelial cells from patients with ...

Convincing evidence has accumulated to identify the Frizzled proteins as receptors for the Wnt growth factors. In parallel, a number of secreted frizzled-like proteins with a conserved N-terminal frizzled motif have been identified. One of these proteins, Frzb-1, binds Wnt-1 and Xwnt-8 proteins and antagonizes Xwnt-8 signaling in Xenopus embryos. Here we report that Frzb-1 blocks Wnt-1 induced ...

Dickkopf proteins are secreted antagonists of the Wnt cell signalling molecules, which have a novel mode of action. Dickkopf1 binds to the LRP5/6 Wnt co-receptor and prevents the formation of active Wnt--Frizzled--LRP5/6 receptor complexes, thus blocking the canonical Wnt--beta-catenin pathway.

Secreted Wnt proteins trigger the intracellular Wnt signaling cascade upon engagement of dedicated Frizzled-Lrp receptor complexes. Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome.

Secreted Wnt morphogens mediate cell-cell communication, but the mechanism of Wnt transfer between cells is unknown. Korkut et al. (2009) report that the transmembrane protein Evi is a versatile carrier that guides Wingless to presynaptic terminals of motor neurons and then escorts it across the synaptic cleft. In postsynaptic muscles, Evi promotes Frizzled-2 trafficking.