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

¹ Department of Pathology, ² Department of Dermatology, and ³ Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

Correspondence to Kathleen J. Green: kgreen{at}northwestern.edu

Dsg1 (desmoglein 1) is a member of the cadherin family of Ca²⁺-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.

Abbreviations used in this paper: Dsc, desmocollin; Dsg, desmoglein; E-cadherin, epithelial cadherin; EGFR, EGF receptor; Erk, extracellular signal-regulated kinase; ETA, exfoliative toxin A; IHC, immunohistochemical; miRNA, microRNA; PG, plakoglobin; RIPA, radioimmunoprecipitation assay; WT, wild type.

© 2009 Getsios et al.
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This article has been cited by other articles:

• Short, B. (2009). Desmoglein directs differentiation. JCB 185: 1130-1130 [Full Text]  

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