Regulation of Endocytosis, Nuclear Translocation, and Signaling of Fibroblast Growth Factor Receptor 1 by E-Cadherin
Open Access
- 1 January 2005
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 16 (1), 14-23
- https://doi.org/10.1091/mbc.e04-09-0845
Abstract
Fibroblast growth factor (FGF) receptors (FGFRs) signal to modulate diverse cellular functions, including epithelial cell morphogenesis. In epithelial cells, E-cadherin plays a key role in cell-cell adhesion, and its function can be regulated through endocytic trafficking. In this study, we investigated the location, trafficking, and function of FGFR1 and E-cadherin and report a novel mechanism, based on endocytic trafficking, for the coregulation of E-cadherin and signaling from FGFR1. FGF induces the internalization of surface FGFR1 and surface E-cadherin, followed by nuclear translocation of FGFR1. The internalization of both proteins is regulated by common endocytic machinery, resulting in cointernalization of FGFR1 and E-cadherin into early endosomes. By blocking endocytosis, we show that this is a requisite, initial step for the nuclear translocation of FGFR1. Overexpression of E-cadherin blocks both the coendocytosis of E-cadherin and FGFR1, the nuclear translocation of FGFR1 and FGF-induced signaling to the mitogen-activated protein kinase pathway. Furthermore, stabilization of surface adhesive E-cadherin, by overexpressing p120ctn, also blocks internalization and nuclear translocation of FGFR1. These data reveal that conjoint endocytosis and trafficking is a novel mechanism for the coregulation of E-cadherin and FGFR1 during cell signaling and morphogenesis.Keywords
This publication has 60 references indexed in Scilit:
- The ins and outs of E-cadherin traffickingTrends in Cell Biology, 2004
- The dynamin superfamily: universal membrane tubulation and fission molecules?Nature Reviews Molecular Cell Biology, 2004
- Cell adhesion and signalling by cadherins and Ig-CAMs in cancerNature Reviews Cancer, 2004
- Contextual Binding of p120 to E-cadherin at the Basolateral Plasma Membrane in Polarized EpitheliaPublished by Elsevier BV ,2003
- Characterization of E-cadherin Endocytosis in Isolated MCF-7 and Chinese Hamster Ovary CellsJournal of Biological Chemistry, 2003
- Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signallingNature, 2002
- Importin β–Mediated Nuclear Import of Fibroblast Growth Factor ReceptorThe Journal of cell biology, 2001
- The Proliferative and Migratory Activities of Breast Cancer Cells Can Be Differentially Regulated by Heparan SulfatesJournal of Biological Chemistry, 2000
- FGFs, heparan sulfate and FGFRs: complex interactions essential for developmentBioEssays, 2000
- Fibroblast Growth Factor Receptors (FGFRs) Localize in Different Cellular CompartmentsPublished by Elsevier BV ,1995