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Review
. 2018 Mar;75(5):785-795.
doi: 10.1007/s00018-017-2654-2. Epub 2017 Sep 14.

The Function of Endocytosis in Wnt Signaling

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Free PMC article
Review

The Function of Endocytosis in Wnt Signaling

Lucy Brunt et al. Cell Mol Life Sci. .
Free PMC article

Abstract

Wnt growth factors regulate one of the most important signaling networks during development, tissue homeostasis and disease. Despite the biological importance of Wnt signaling, the mechanism of endocytosis during this process is ill described. Wnt molecules can act as paracrine signals, which are secreted from the producing cells and transported through neighboring tissue to activate signaling in target cells. Endocytosis of the ligand is important at several stages of action: One central function of endocytic trafficking in the Wnt pathway occurs in the source cell. Furthermore, the β-catenin-dependent Wnt ligands require endocytosis for signal activation and to regulate gene transcription in the responding cells. Alternatively, Wnt/β-catenin-independent signaling regulates endocytosis of cell adherence plaques to control cell migration. In this comparative review, we elucidate these three fundamental interconnected functions, which together regulate cellular fate and cellular behavior. Based on established hypotheses and recent findings, we develop a revised picture for the complex function of endocytosis in the Wnt signaling network.

Keywords: Cytonemes; Endocytosis; Exosomes; Planar cell polarity; Signal activation; Wnt.

Figures

Fig. 1
Fig. 1
Endocytosis-regulated Wnt/Wg secretion. After formation and lipid modification of the ligand (1), Evi/Wl transports Wnt/Wg to the plasma membrane. The ligand induces either a cytoneme (2) or it gets re-endocytosed and packaged in exosomes (3) for the subsequent secretion (4). Re-endocytosis and transport of Evi/Wl to the Golgi close the loop (5)
Fig. 2
Fig. 2
Endocytosis mechanism essential for Wnt/β-catenin signaling. In the Wnt off state, β-catenin is continuously degraded. Wnt presentation to the receiving cell leads to signalosome formation (1). The signalosome is taken up into the cell (2). Disassembly of the Clathrin lattice (blue dashed line) leads to separation of the endocytic vesicles carrying the ligand and the β-catenin/destruction complex, which becomes deactivated (3). Next, β-catenin accumulates and starts to regulate the transcription program in the nucleus (4)
Fig. 3
Fig. 3
PCP signaling-regulated cell migration by endocytosis of adhesion plaques. Adhesion plaques serve as anchors to neighboring cells or substrates (1). Noncanonical Wnt signaling activates the internalization of the plaque components cadherin and protocadherin, predominantly in the rear of the cell (2). Cadherins are routed through the endocytic pathway from Rab5 early endosomes to Rab4/11 recycling endosomes (3). This allows for the assembly of new anchor points at the front of the cell. Cadherins are also routed for degradation to Rab7-positive endosomes and Lamp1 lysosomes (4). The differential rate between recycling and degradation determines the amount of Cadherin available for adhesion

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References

    1. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149:1192–1205. doi: 10.1016/j.cell.2012.05.012. - DOI - PubMed
    1. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810. doi: 10.1146/annurev.cellbio.20.010403.113126. - DOI - PubMed
    1. Li VSW, Ng SS, Boersema PJ, et al. Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245–1256. doi: 10.1016/j.cell.2012.05.002. - DOI - PubMed
    1. Posokhova E, Shukla A, Seaman S, et al. GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Rep. 2015;10:123–130. doi: 10.1016/j.celrep.2014.12.020. - DOI - PMC - PubMed
    1. Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 2012;13:767–779. doi: 10.1038/nrm3470. - DOI - PubMed

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