Further Development 4.12: Endosome Internalization:Morphogen Gradients Can Be Created by Literally Passing from One Cell to Another

Cell-to-Cell Communication: Mechanisms of Morphogenesis

The type and number of receptors that a cell displays at its cell surface represent its potential for response. Endocytosis is one mechanism used to eliminate a receptor at the membrane. Recent studies are revealing that internalization of ligand-receptor complexes into membrane-bound vesicles called endosomes is a common mechanism in paracrine signaling. When Wnt binds to its receptors, the β-catenin destruction complex binds to the receptor, and the entire complex (including the receptor and its bound Wnt) is internalized in endosomes (Figure 1; Taelman et al. 2010; Niehrs 2012). This process removes the complex, targets it for degradation, and enables the survival of β-catenin. The internalization of the signaling complex appears to be critical for the accumulation of β-catenin, and proteins that aid in this endocytosis (such as R-spondins; see Figure 4.26) make the Wnt pathway more efficient (Ohkawara et al. 2011). Similarly, Hedgehog-Patched complexes and FGF-FGFR complexes are also internalized in endosomes and targeted for degradation, a process that is required for proper limb development (Briscoe and Thérond 2013; Handschuh et al. 2014; Hsia et al. 2015).

Figure 1 A Wnt pathway: packaging the β-catenin destruction apparatus into endosomes. A major mechanism for separating β-catenin from enzymes that would otherwise destroy it is to package the complex in membrane-bound vesicles called endosomes. When Wnt binds to Frizzled, Frizzled can bind the destruction complex (DC); the entire complex (including the bound Wnt and its receptor) is internalized, allowing β-catenin to accumulate rather than being degraded. (After Taelman et al. 2010.)

Literature Cited

Briscoe, J. and P. P. Thérond. 2013. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat. Rev. Mol. Cell Biol. 14: 416–429.
PubMed Link

Handschuh, K. and 21 others. 2014. ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling. Cell Rep. 9: 674–687.
PubMed Link

Hsia, E. Y., Y. Gui and X. Zheng. 2015. Regulation of Hedgehog signaling by ubiquitination. Front. Biol. 10: 203–220.
PubMed Link

Niehrs, C. 2012. The complex world of Wnt receptor signalling. Nat. Rev. Mol. Cell Biol. 13: 767–779.
PubMed Link

Ohkawara, B., A. Glinka and C. Niehrs. 2011. Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis. Dev. Cell 20: 303–314.
PubMed Link

Taelman, V. F., R. Dobrowolski, J. L. Plouhinec, L. C. Fuentealba, P. P. Vorwald, I. Gumper, D. D. Sabatini and E. M. De Robertis. 2010. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143: 1136–1148.
PubMed Link

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