Desmosomal glycoprotein DGI, a component of intercellular desmosome junctions, is related to the cadherin family of cell adhesion molecules.

Abstract

Among the variety of specialized intercellular junctions, those of the adherens type have the most obvious association with cytoskeletal elements. This may be with the actin microfilanent system as in the zonula adherens or with intermediate ifiaments as in the macula adherens, or desmosome. In the former case, it is clear that transmembrane glycoproteins of the cadherin family are important adhesive components of the molecular assembly. We now show for desmosomes that a major glycoprotein component (desmosomal glycoprotein DGI) has extensive homology with the cadherins, defining an extended fmily, but also has unique features in its cytoplasmic domain that are likely to be relevant to the association with intermediate rather than actin filaments. A novel 282-residue extension contains repeats of --29 amino acid residues predicted to have an antiparallel P-sheet structure, followed by a glycine-rich sequence. As in the cadherins, the extracellular domain contains possible Ca2+-binding sequences and a potential protease processing site. The cell adhesion recognition region (His-Ala-Val) METHODSGeneration and Screening ofAntibodies. Desmosomes were isolated from bovine muzzle epidermis (4). Rabbit anti-DGI serum was generated against DGI purified by SDS/PAGE and electroelution; its specificity was similar to the guinea pig sera previously described (4). The tTo whom reprint requests should be addressed. §The sequence reported in this paper has been deposited in the GenBank data base (accession no. X56654). 4796The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma

“…Exon-intron structure of the DSG1 gene Using primers from the DSG1 cDNA sequence 14 in PCR on genomic DNA, we cloned all of the exons and introns, and sequenced the exon-intron boundaries (Table 1) and sufficient intron sequence to generate intron primers ( Table 2). Intron position is remarkably conserved amongst the classical cadherins 15 ± 17 and in the extracellular domain of the desmogleins (bovine DSG1 18 and human DSG3 19 ) and the desmocollins (human DSC2 20 ) and DSG1 is no exception, the position of the introns being completely conserved compared with those of bovine DSG1 even where the amino acids are different.…”

Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus

“…4 Pemphigus is a group of rare and severe cutaneous organ-specific autoimmune diseases, characterized by the production of autoantibodies directed against desmosomal adhesion molecules expressed by keratinocytes 5 and responsible for the formation of intraepidermal blisters. In the sporadic form of pemphigus foliaceus (PF) and fogo selvagem, its endemic form observed in certain areas of Brazil, pathogenic autoantibodies bind to desmoglein 1 (DSG1), [6][7][8][9][10][11][12] a glycoprotein that mediates cell adhesion in the superficial layers of the epidermis. MHC class II loci have been demonstrated to participate in susceptibility to both forms of PF.…”

Visualisation by electron microscopy of the unique part of the cytoplasmic domain of a desmoglein, a cadherin‐like protein of the desmosome type of cell junction

“…A 1204 bp StyI-XhoI fragment (2364 -3567 bp in EMBL database sequence X56654; residues 714-1000 of the mature protein) [10,11] located at the 3' end of the human DSG1 gene, starting with the amino acid sequence LGKES and ending in the 3'-untranslated region, was filled-in using the Klenow fragment of DNA polymerase and subcloned into the StuI site of the pMal-c expression vector [12] (New England Biolabs), thus retaining the reading frame. This sequence starts just prior to the end of homology with the classical cadherins, and contains the remainder of the cytoplasmic domain including the region of desmoglein-unique repeats.…”