A Critical Role for Endocytosis in Wnt Signaling

Overview

Journal BMC Cell Biol

Publisher Biomed Central

Specialty Cell Biology

Date 2006 Jul 11

PMID 16824228

Citations 116

Authors

Jeremy T Blitzer

Roel Nusse

Affiliations

Soon will be listed here.

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.

Citing Articles

Wnt signalosomes: What we know that we do not know.

Hartmann H, Siddiqui G, Bryant J, Robbins D, Weiss V, Ahmed Y Bioessays. 2024; 47(2):e2400110.

PMID: 39520379 PMC: 11755710. DOI: 10.1002/bies.202400110.

The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development.

Ensing J, Ide A, Gilliland C, Tsurho V, Caza I, Stratman A bioRxiv. 2024; .

PMID: 39484584 PMC: 11527353. DOI: 10.1101/2024.10.25.620301.

Stimulating Wnt signaling reveals context-dependent genetic effects on gene regulation in primary human neural progenitors.

Matoba N, Le B, Valone J, Wolter J, Mory J, Liang D Nat Neurosci. 2024; 27(12):2430-2442.

PMID: 39349663 PMC: 11633645. DOI: 10.1038/s41593-024-01773-6.

ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner.

Xiong L, Guo H, Pan J, Ren X, Lee D, Chen L Bone Res. 2024; 12(1):33.

PMID: 38811544 PMC: 11137048. DOI: 10.1038/s41413-024-00335-7.

Regulation of YAP and Wnt signaling by the endosomal protein MAMDC4.

Cox C, Wu M, Padilla-Rodriguez M, Blum I, Momtaz S, Mitchell S PLoS One. 2024; 19(5):e0296003.

PMID: 38787854 PMC: 11125477. DOI: 10.1371/journal.pone.0296003.

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