title: Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis.
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.
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Spiro
authors: S
authors: Getsios
authors: Cory L
authors: CL
authors: Simpson
authors: Shin-ichiro
authors: S
authors: Kojima
authors: Robert
authors: R
authors: Harmon
authors: Linda J
authors: LJ
authors: Sheu
authors: Rachel L
authors: RL
authors: Dusek
authors: Mona
authors: M
authors: Cornwell
authors: Kathleen J
authors: KJ
authors: Green
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D051183:Desmoglein 1; D035683:MicroRNAs; D020033:Protein Isoforms; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases