Disease relevance of DSG1

• A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus [1].
• On the other hand, some pemphigus foliaceus (Pf) sera exhibited reactivity with a 150-kD protein, which is most likely desmoglein I, in both the human epidermal extract and the bovine desmosome preparation, but no Pf serum reacted with this antigen in the squamous carcinoma cell extract [2].
• Four kinds of anti-GD3 monoclonal antibodies, DSG-1, -2, -3, and -4, of the IgM class were obtained by the immunization of BALB/c mice with enzootic bovine leukosis tumor tissue-derived ganglioside GD3 inserted into liposomes with Salmonella minnesota R595 lipopolysaccharides [3].

High impact information on DSG1

• Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes [4].
• In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I [4].
• The extracellular domain of dg3 shows 39.4% protein sequence identity with bovine N-cadherin and 28.4% identity with the other major desmosomal glycoprotein, dg1, or desmoglein [5].
• The two major glycoprotein families (DGI and DGII/III) were both found to be synthesized with co-translational addition of 2-4 high mannose cores later processed into complex type chains [6].
• Identification of amino acid sequence motifs in desmocollin, a desmosomal glycoprotein, that are required for plakoglobin binding and plaque formation [7].

Chemical compound and disease context of DSG1

• The major antibody binding regions of desmoglein 1 (Dsg1) in pemphigus foliaceus and pemphigus vulgaris were examined using cDNA-encoded fusion proteins combining glutathione S-transferase with various domains of bovine Dsg1, namely, the extracellular regions EC1-2, EC3-5, EC1-5, and the entire intracellular region IC [8].

Biological context of DSG1

• Using one of these antibodies (DG3.10), a peptide was isolated from a proteolytic digest of desmoglein purified from isolated bovine muzzle demosomes, and its amino acid sequence was determined [9].
• We conclude that desmoglein is a member of the cadherin family of cell adhesion glycoproteins which is characterized by an unusually long cytoplasmic domain which exceeds those of the cadherins by more than 275 amino acids, contains special repetitive elements and spans the desmosomal plaque at least once [9].
• This topological information, together with the identification of a single hydrophobic region of sufficient length to provide a transmembrane segment and of several extended regions showing high sequence homology to various cadherins, has allowed the construction of a model of the molecular organization of desmoglein [9].
• The isolation of the complete cDNA has allowed the cloning of a desmoglein cDNA construct, which under the control of the human beta-actin promoter, was successfully used in cell transfection [10].
• T1alpha expression is markedly inhibited in both DG1 and DG4 cultures, consistent with both inhibition and reversal of the transition toward the AT1 cell phenotype [11].

Anatomical context of DSG1

• Polymorphism was found in a sequence of DSG1 encoding protein proximal to the external face of the plasma membrane [12].
• Desmoglein is a major adhesive component of the desmosome [13].
• In the course of these studies we have identified, in colon carcinoma and other simple epithelial cells, another kind of desmoglein which by partial cDNA-derived sequence and by Southern blotting is clearly the product of a different gene [10].
• Desmosomes are intercellular junctions that contain two major kinds of transmembrane glycoproteins, desmoglein and desmocollins I and II, involved in cell-cell adhesion [14].
• This region of Dsg1 sequence shows significant similarity to the catenin-binding domain of classical cadherins, suggesting a common mechanism for the association of plakoglobin with desmosomes and adherens junctions [15].

Associations of DSG1 with chemical compounds

• Expression of desmoglein and transglutaminase was increased by Ca2+ stimulation, whereas beta1 integrin expression was decreased in response to increasing concentrations of Ca2+ [16].

Other interactions of DSG1

• Amino acid sequence comparisons have revealed that desmocollin is highly homologous to members of the cadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific cadherin [17].

Analytical, diagnostic and therapeutic context of DSG1

• Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots [4].
• In analyses of cDNA sequences and Northern blot experiments we have now found that both desmoglein and desmocollins are not unique gene products but occur in different subtypes produced from different genes [14].
• While the desmoglein genes can be differentially expressed in different cell types, both type 1 and type 2 desmocollins can coexist in the same cells of certain stratified epithelia as shown by in situ hybridization [14].
• To further characterize this antigen/antibody system, the 80-kD pemphigus foliaceus antigen solubilized from a bovine epidermal envelope extract was purified by affinity chromatography using a pemphigus foliaceus patient's immunoglobulin (Ig)G immobilized on agarose [18].
• Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG anti-intercellular antibodies that recognized the 150 kd desmoglein (pemphigus foliaceus antigen) in bovine desmosome preparation [19].

References