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Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking
The reggie/flotillin proteins are implicated in membrane trafficking and, together with the cellular prion protein (PrP), in the recruitment of E-cadherin to cell contact sites. Here, we demonstrate that reggies, as well as PrP down-regulation, in epithelial A431 cells cause overlapping processes an...
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/PMC3350547/ https://www.ncbi.nlm.nih.gov/pubmed/22438585 http://dx.doi.org/10.1091/mbc.E11-12-1006 |
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author | Solis, Gonzalo P. Schrock, Yvonne Hülsbusch, Nikola Wiechers, Marianne Plattner, Helmut Stuermer, Claudia A. O. |
author_facet | Solis, Gonzalo P. Schrock, Yvonne Hülsbusch, Nikola Wiechers, Marianne Plattner, Helmut Stuermer, Claudia A. O. |
author_sort | Solis, Gonzalo P. |
collection | PubMed |
description | The reggie/flotillin proteins are implicated in membrane trafficking and, together with the cellular prion protein (PrP), in the recruitment of E-cadherin to cell contact sites. Here, we demonstrate that reggies, as well as PrP down-regulation, in epithelial A431 cells cause overlapping processes and abnormal formation of adherens junctions (AJs). This defect in cell adhesion results from reggie effects on Src tyrosine kinases and epidermal growth factor receptor (EGFR): loss of reggies reduces Src activation and EGFR phosphorylation at residues targeted by Src and c-cbl and leads to increased surface exposure of EGFR by blocking its internalization. The prolonged EGFR signaling at the plasma membrane enhances cell motility and macropinocytosis, by which junction-associated E-cadherin is internalized and recycled back to AJs. Accordingly, blockage of EGFR signaling or macropinocytosis in reggie-deficient cells restores normal AJ formation. Thus, by promoting EGFR internalization, reggies restrict the EGFR signaling involved in E-cadherin macropinocytosis and recycling and regulate AJ formation and dynamics and thereby cell adhesion. |
format | Online Article Text |
id | pubmed-3350547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33505472012-07-30 Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking Solis, Gonzalo P. Schrock, Yvonne Hülsbusch, Nikola Wiechers, Marianne Plattner, Helmut Stuermer, Claudia A. O. Mol Biol Cell Articles The reggie/flotillin proteins are implicated in membrane trafficking and, together with the cellular prion protein (PrP), in the recruitment of E-cadherin to cell contact sites. Here, we demonstrate that reggies, as well as PrP down-regulation, in epithelial A431 cells cause overlapping processes and abnormal formation of adherens junctions (AJs). This defect in cell adhesion results from reggie effects on Src tyrosine kinases and epidermal growth factor receptor (EGFR): loss of reggies reduces Src activation and EGFR phosphorylation at residues targeted by Src and c-cbl and leads to increased surface exposure of EGFR by blocking its internalization. The prolonged EGFR signaling at the plasma membrane enhances cell motility and macropinocytosis, by which junction-associated E-cadherin is internalized and recycled back to AJs. Accordingly, blockage of EGFR signaling or macropinocytosis in reggie-deficient cells restores normal AJ formation. Thus, by promoting EGFR internalization, reggies restrict the EGFR signaling involved in E-cadherin macropinocytosis and recycling and regulate AJ formation and dynamics and thereby cell adhesion. The American Society for Cell Biology 2012-05-15 /pmc/articles/PMC3350547/ /pubmed/22438585 http://dx.doi.org/10.1091/mbc.E11-12-1006 Text en © 2012 Solis 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 Solis, Gonzalo P. Schrock, Yvonne Hülsbusch, Nikola Wiechers, Marianne Plattner, Helmut Stuermer, Claudia A. O. Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title | Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title_full | Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title_fullStr | Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title_full_unstemmed | Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title_short | Reggies/flotillins regulate E-cadherin–mediated cell contact formation by affecting EGFR trafficking |
title_sort | reggies/flotillins regulate e-cadherin–mediated cell contact formation by affecting egfr trafficking |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350547/ https://www.ncbi.nlm.nih.gov/pubmed/22438585 http://dx.doi.org/10.1091/mbc.E11-12-1006 |
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