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PMID: 21289093 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin.

Molecular biology of the cell ·Vol. 22 ·No. 7 ·2011-04-00 ·Pages 940-53

Yeh YC, Wu CC, Wang YK, Tang MJ

Abstract

Discoidin domain receptor 1 (DDR1) promotes E-cadherin-mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation.

MeSH Terms
Animals Cadherins/metabolism Cell Adhesion/physiology Cell Dedifferentiation/physiology Cell Differentiation/physiology Cell Line Cell Membrane/metabolism Cell Movement Discoidin Domain Receptors Epithelial Cells/cytology,physiology Humans Intercellular Junctions/metabolism Mice Mice, Knockout Receptor Protein-Tyrosine Kinases/genetics,metabolism Receptors, Mitogen/genetics,metabolism cdc42 GTP-Binding Protein/metabolism
Chemicals
Cadherins Receptors, Mitogen Discoidin Domain Receptors Receptor Protein-Tyrosine Kinases cdc42 GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yeh Yi-Chun
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Wu Chia-Ching
Wang Yang-Kao
Tang Ming-Jer
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.E10-08-0678
Published
2011-04-00
Epub
2011-00-02
Pages
940-53
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC3069019
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.E10-08-0678 PMC Full Text View journal details
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