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Open Access Highly Accessed Open Badges 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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BMC Cell Biology 2006, 7:28  doi:10.1186/1471-2121-7-28

Published: 6 July 2006



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.


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.


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.