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Open Access Highly Accessed Research article

A critical role for endocytosis in Wnt signaling

Jeremy T Blitzer and Roel Nusse*

Author affiliations

Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA

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Citation and License

BMC Cell Biology 2006, 7:28  doi:10.1186/1471-2121-7-28

Published: 6 July 2006

Abstract

Background

The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation.

Results

We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression.

Conclusion

A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components.