Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion

Ungewiss, Hanna; Rötzer, Vera; Meir, Michael; Fey, Christina; Diefenbacher, Markus; Schlegel, Nicolas und Waschke, Jens (2018): Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. In: Cellular and Molecular Life Sciences, Bd. 75, Nr. 22: S. 4251-4268

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1420-682X
• Sprache: Englisch