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Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion
We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin–catenin complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364174/ https://www.ncbi.nlm.nih.gov/pubmed/22513089 http://dx.doi.org/10.1091/mbc.E11-12-1060 |
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author | Petrova, Yuliya I. Spano, MarthaJoy M. Gumbiner, Barry M. |
author_facet | Petrova, Yuliya I. Spano, MarthaJoy M. Gumbiner, Barry M. |
author_sort | Petrova, Yuliya I. |
collection | PubMed |
description | We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin–catenin complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able to distinguish the inactive and active states of E-cadherin at the cell surface by using a special set of monoclonal antibodies (mAbs). Another set of mAbs binds E-cadherin and strongly activates adhesion. In other epithelial cell types these activating mAbs inhibit growth factor–induced down-regulation of adhesion and epithelial morphogenesis, indicating that these phenomena are also controlled by E-cadherin activity at the cell surface. Both types of mAbs recognize conformational epitopes at different interfaces between extracellular cadherin repeat domains (ECs), especially near calcium-binding sites. Activation also induces p120-catenin dephosphorylation, as well as changes in the cadherin cytoplasmic domain. Moreover, phospho-site mutations indicate that dephosphorylation of specific Ser/Thr residues in the N-terminal domain of p120-catenin mediate adhesion activation. Thus physiological regulation of the adhesive state of E-cadherin involves physical and/or conformational changes in the EC interface regions of the ectodomain at the cell surface that are mediated by catenin-associated changes across the membrane. |
format | Online Article Text |
id | pubmed-3364174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33641742012-08-16 Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion Petrova, Yuliya I. Spano, MarthaJoy M. Gumbiner, Barry M. Mol Biol Cell Articles We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin–catenin complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able to distinguish the inactive and active states of E-cadherin at the cell surface by using a special set of monoclonal antibodies (mAbs). Another set of mAbs binds E-cadherin and strongly activates adhesion. In other epithelial cell types these activating mAbs inhibit growth factor–induced down-regulation of adhesion and epithelial morphogenesis, indicating that these phenomena are also controlled by E-cadherin activity at the cell surface. Both types of mAbs recognize conformational epitopes at different interfaces between extracellular cadherin repeat domains (ECs), especially near calcium-binding sites. Activation also induces p120-catenin dephosphorylation, as well as changes in the cadherin cytoplasmic domain. Moreover, phospho-site mutations indicate that dephosphorylation of specific Ser/Thr residues in the N-terminal domain of p120-catenin mediate adhesion activation. Thus physiological regulation of the adhesive state of E-cadherin involves physical and/or conformational changes in the EC interface regions of the ectodomain at the cell surface that are mediated by catenin-associated changes across the membrane. The American Society for Cell Biology 2012-06-01 /pmc/articles/PMC3364174/ /pubmed/22513089 http://dx.doi.org/10.1091/mbc.E11-12-1060 Text en © 2012 Petrova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Petrova, Yuliya I. Spano, MarthaJoy M. Gumbiner, Barry M. Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title | Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title_full | Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title_fullStr | Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title_full_unstemmed | Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title_short | Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
title_sort | conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364174/ https://www.ncbi.nlm.nih.gov/pubmed/22513089 http://dx.doi.org/10.1091/mbc.E11-12-1060 |
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