Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion |
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Authors: | Hanna Ungewiß Vera Rötzer Michael Meir Christina Fey Markus Diefenbacher Nicolas Schlegel Jens Waschke |
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Institution: | 1.Department I, Institute of Anatomy and Cell Biology,Ludwig Maximilians University Munich,Munich,Germany;2.Department of General, Visceral, Vascular and Paediatric Surgery,Julius-Maximilians-Universit?t,Würzburg,Germany;3.Department for Tissue Engineering and Regenerative Medicine,University Hospital Würzburg,Würzburg,Germany;4.Department of Biochemistry and Molecular Biochemistry,University of Würzburg,Würzburg,Germany |
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Abstract: | Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell–cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion. |
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