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BMC Cell Biol. 2006 Jul 6;7:28.

A critical role for endocytosis in Wnt signaling.

Author information

1
Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. jblitzer@stanford.edu

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 beta-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.

PMID:
16824228
PMCID:
PMC1534015
DOI:
10.1186/1471-2121-7-28
[Indexed for MEDLINE]
Free PMC Article

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