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

H Ungewiß, V Rötzer, M Meir, C Fey… - Cellular and molecular …, 2018 - Springer
H Ungewiß, V Rötzer, M Meir, C Fey, M Diefenbacher, N Schlegel, J Waschke
Cellular and molecular life sciences, 2018Springer
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 …
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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