Reggies/Flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking

The reggie/flotillin proteins were 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 downregulation in epithelial A431 cells caused overlapping processes and abnormal formation of adherens junctions (AJs). This defect in cell adhesion resulted from the reggie effects on Src tyrosine kinases and epidermal growth factor receptor (EGFR): loss of reggies reduced Src activation and EGFR phosphorylation at residues targeted by Src and c-cbl, and led to increased surface-exposure of EGFR by blocking its internalization. The prolonged EGFR signaling at the plasma membrane enhanced cell motility and macropinocytosis through which junction-associated E-cadherin is internalized and recycled back to AJs. Accordingly, blockage of EGFR signaling or macropinocytosis in reggie-deficient cells restored normal AJ formation. Thus, by promoting EGFR internalization, reggies restrict the EGFR signaling involved in E-cadherin macropinocytosis and recycling, regulate AJ formation and dynamics and thereby cell adhesion.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

SOLIS, Gonzalo, Yvonne SCHROCK, Nikola HÜLSBUSCH, Marianne F. WIECHERS, Helmut PLATTNER, Claudia STÜRMER, 2012. Reggies/Flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking. In: Molecular Biology of the Cell. 2012, 23(10), pp. 1812-1825. ISSN 1059-1524. eISSN 1939-4586. Available under: doi: 10.1091/mbc.E11-12-1006

BibTex

@article{Solis2012-05Reggi-19104,
  year={2012},
  doi={10.1091/mbc.E11-12-1006},
  title={Reggies/Flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking},
  number={10},
  volume={23},
  issn={1059-1524},
  journal={Molecular Biology of the Cell},
  pages={1812--1825},
  author={Solis, Gonzalo and Schrock, Yvonne and Hülsbusch, Nikola and Wiechers, Marianne F. and Plattner, Helmut and Stürmer, Claudia}
}

RDF

<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/19104">
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/19104/2/Stuermer_191040.pdf"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/19104/2/Stuermer_191040.pdf"/>
    <dc:creator>Stürmer, Claudia</dc:creator>
    <dc:creator>Hülsbusch, Nikola</dc:creator>
    <dc:language>eng</dc:language>
    <dc:contributor>Hülsbusch, Nikola</dc:contributor>
    <dcterms:title>Reggies/Flotillins regulate E-cadherin-mediated cell contact formation by affecting EGFR trafficking</dcterms:title>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Wiechers, Marianne F.</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Solis, Gonzalo</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-06-13T12:55:30Z</dcterms:available>
    <dcterms:bibliographicCitation>Publ. in: Molucular Biology of the Cell ; 23 (2012), 10. - S. 1812-1825</dcterms:bibliographicCitation>
    <dc:creator>Wiechers, Marianne F.</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/19104"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-06-13T12:55:30Z</dc:date>
    <dc:contributor>Plattner, Helmut</dc:contributor>
    <dcterms:issued>2012-05</dcterms:issued>
    <dc:creator>Plattner, Helmut</dc:creator>
    <dc:creator>Solis, Gonzalo</dc:creator>
    <dcterms:abstract xml:lang="eng">The reggie/flotillin proteins were 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 downregulation in epithelial A431 cells caused overlapping processes and abnormal formation of adherens junctions (AJs). This defect in cell adhesion resulted from the reggie effects on Src tyrosine kinases and epidermal growth factor receptor (EGFR): loss of reggies reduced Src activation and EGFR phosphorylation at residues targeted by Src and c-cbl, and led to increased surface-exposure of EGFR by blocking its internalization. The prolonged EGFR signaling at the plasma membrane enhanced cell motility and macropinocytosis through which junction-associated E-cadherin is internalized and recycled back to AJs. Accordingly, blockage of EGFR signaling or macropinocytosis in reggie-deficient cells restored normal AJ formation. Thus, by promoting EGFR internalization, reggies restrict the EGFR signaling involved in E-cadherin macropinocytosis and recycling, regulate AJ formation and dynamics and thereby cell adhesion.</dcterms:abstract>
    <dc:contributor>Stürmer, Claudia</dc:contributor>
    <dc:rights>terms-of-use</dc:rights>
    <dc:creator>Schrock, Yvonne</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Schrock, Yvonne</dc:contributor>
  </rdf:Description>
</rdf:RDF>

Universitätsbibliographie

Ja