Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis

Spiro Getsios, Cory L. Simpson, Shin Ichiro Kojima, Robert Harmon, Linda J. Sheu, Rachel L. Dusek, Mona Cornwell, Kathleen J. Green

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Dsg1 (desmoglein 1) is a member of the cadherin family of Ca 2+-dependent cell adhesion molecules that is first expressed in the epidermis as keratinocytes transit out of the basal layer and becomes concentrated in the uppermost cell layers of this stratified epithelium. In this study, we show that Dsg1 is not only required for maintaining epidermal tissue integrity in the superficial layers but also supports keratinocyte differentiation and suprabasal morphogenesis. Dsg1 lacking N-terminal ectodomain residues required for adhesion remained capable of promoting keratinocyte differentiation. Moreover, this capability did not depend on cytodomain interactions with the armadillo protein plakoglobin or coexpression of its companion suprabasal cadherin, Dsc1 (desmocollin 1). Instead, Dsg1 was required for suppression of epidermal growth factor receptor-Erk1/2 (extracellular signal-regulated kinase 1/2) signaling, thereby facilitating keratinocyte progression through a terminal differentiation program. In addition to serving as a rigid anchor between adjacent cells, this study implicates desmosomal cadherins as key components of a signaling axis governing epithelial morphogenesis.

Original languageEnglish (US)
Pages (from-to)1243-1258
Number of pages16
JournalJournal of Cell Biology
Volume185
Issue number7
DOIs
StatePublished - Jun 29 2009

ASJC Scopus subject areas

  • Cell Biology

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