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

Ungewiß, H.; Rötzer, V.; Meir, M.; Fey, C.; Diefenbacher, M.; Schlegel, N.; Waschke, J.

Cellular and Molecular Life Sciences: Cmls 75(22): 4251-4268

2018


ISSN/ISBN: 1420-9071
PMID: 29980799
DOI: 10.1007/s00018-018-2869-x
Accession: 058946169

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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