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).
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
All the material on this website is protected by copyright. It may not be reproduced in any form without permission from the copyright holder.