Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Solis, Gonzalo P., Schrock, Yvonne, Hülsbusch, Nikola, Wiechers, Marianne, Plattner, Helmut, Stuermer, Claudia A. O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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
_version_ 1782232686769733632
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
work_keys_str_mv AT solisgonzalop reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking
AT schrockyvonne reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking
AT hulsbuschnikola reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking
AT wiechersmarianne reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking
AT plattnerhelmut reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking
AT stuermerclaudiaao reggiesflotillinsregulateecadherinmediatedcellcontactformationbyaffectingegfrtrafficking