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

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...

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Detalles Bibliográficos
Autores principales: Getsios, Spiro, Simpson, Cory L., Kojima, Shin-ichiro, Harmon, Robert, Sheu, Linda J., Dusek, Rachel L., Cornwell, Mona, Green, Kathleen J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712955/
https://www.ncbi.nlm.nih.gov/pubmed/19546243
http://dx.doi.org/10.1083/jcb.200809044
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author Getsios, Spiro
Simpson, Cory L.
Kojima, Shin-ichiro
Harmon, Robert
Sheu, Linda J.
Dusek, Rachel L.
Cornwell, Mona
Green, Kathleen J.
author_facet Getsios, Spiro
Simpson, Cory L.
Kojima, Shin-ichiro
Harmon, Robert
Sheu, Linda J.
Dusek, Rachel L.
Cornwell, Mona
Green, Kathleen J.
author_sort Getsios, Spiro
collection PubMed
description 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.
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spelling pubmed-27129552009-12-29 Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis Getsios, Spiro Simpson, Cory L. Kojima, Shin-ichiro Harmon, Robert Sheu, Linda J. Dusek, Rachel L. Cornwell, Mona Green, Kathleen J. J Cell Biol Research Articles 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. The Rockefeller University Press 2009-06-29 /pmc/articles/PMC2712955/ /pubmed/19546243 http://dx.doi.org/10.1083/jcb.200809044 Text en © 2009 Getsios et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Getsios, Spiro
Simpson, Cory L.
Kojima, Shin-ichiro
Harmon, Robert
Sheu, Linda J.
Dusek, Rachel L.
Cornwell, Mona
Green, Kathleen J.
Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title_full Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title_fullStr Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title_full_unstemmed Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title_short Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
title_sort desmoglein 1–dependent suppression of egfr signaling promotes epidermal differentiation and morphogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712955/
https://www.ncbi.nlm.nih.gov/pubmed/19546243
http://dx.doi.org/10.1083/jcb.200809044
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