Disease relevance of DSC1

• RESULTS: None of 45 sera of classical pemphigus showed either IgG or IgA antibodies to any Dsc [1].
• BACKGROUND: We have shown previously that human desmocollin (Dsc) 1 is recognized by IgA autoantibodies of subcorneal pustular dermatosis (SPD) type IgA pemphigus [1].
• IgA antikeratinocyte surface autoantibodies from two types of intercellular IgA vesiculopustular dermatosis recognize distinct isoforms of desmocollin [2].
• Desmocollin switching in colorectal cancer [3].
• OBJECTIVES: To investigate this by producing recombinant proteins consisting of the entire extracellular domains of human Dsc1, 2 and 3 in baculovirus, and to use them to establish an enzyme-linked immunosorbent assay (ELISA) [1].

High impact information on DSC1

• The results show that the tail of the long splice form a of Dsc, but not its shorter splice form b, contains sufficient information to recruit desmoplakin and plakoglobin to connexon membrane paracrystals (gap junctions) and to form a novel kind of plaque at which cytokeratin IFs attach [4].
• Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion [5].
• These assays have shown that plakoglobin associates most tightly with the C-domain of Dsg, to a lesser degree with that of Dsc and only weakly with the C-domain of E-cadherin [6].
• The 115-44-kD glycopolypeptides were also recognized by antisera raised against desmoglein II/desmocollin glycoproteins isolated from bovine spinous layer desmosomes [7].
• This adhesion is specifically blocked by short peptides corresponding to the putative cell adhesion recognition sites of desmocollin and desmoglein [8].

Biological context of DSC1

• The DSC1 gene comprises 17 exons spanning approximately 33 kb on 18q12.1, and the DSC3 gene comprises 17 exons spanning approximately 49 kb on 18q12 [9].
• Cloning of the cDNA (DSC1) coding for human type 1 desmocollin and its assignment to chromosome 18 [10].
• The conservation of close genetic linkage may be of trivial importance related to the recent duplication of these genes or may be because there is a region within the locus that is involved in coordinating the expression of the desmoglein and desmocollin genes [11].
• A YAC contig joining the desmocollin and desmoglein loci on human chromosome 18 and ordering of the desmocollin genes [11].
• We have sought to analyse desmocollin function by reducing the amount of protein using antisense gene expression in the widely studied Madin-Darby canine kidney (MDCK) cell line [12].

Anatomical context of DSC1

• DSC1 was not detected in any of the nonkeratinizing human epithelia examined (buccal mucosa, cervix, esophagus), indicating that it is specific for the keratinizing epithelium of the epidermis [13].
• Mouse cDNA clones coding for a desmocollin and a desmoglein, desmosomal cadherins that are putative adhesion molecules of the desmosome type of cell-cell junction characteristically found in epithelial tissues, have been isolated and sequenced [14].
• Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study [15].
• Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes [16].
• These findings lead us to speculate that Dsc interacts with components of the adherens junctions through beta-catenin, and plays a role in nucleating desmosomes after the adherens junctions have been established [16].

Associations of DSC1 with chemical compounds

• Using alanine scanning mutagenesis and the co-immunoprecipitation assay we identified nine hydrophobic amino acids within the arm repeats 1-3 of plakoglobin, that are required for binding to Dsg and Dsc [17].
• Reduced desmocollin expression may indicate compromised desmosomal adhesion, leading to the skin fragility that results from retinoid treatment [18].
• Voltage-gated sodium channel genes hscp and hDSC1 of Heliothis virescens F. genomic organization [19].
• By immunogold post embedding technique, we studied in anagen HFs the modulation of the synthesis of desmocollin 1 (Dsc1), a transmembrane glycoprotein specifically synthesized in the IRS and in the companion layer [20].

Other interactions of DSC1

• All of the known desmoglein and desmocollin isoforms, which have differing tissue and developmental distributions, are coded by very closely linked genes at 18q12 [11].
• It was negative for desmocollin 1 but strongly immunopositive for desmoglein 1 suprabasally and for desmoglein 2 in the basal cells [21].
• Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2 [22].
• We show that inhibition of SERCA by thapsigargin in normal human keratinocytes impairs the trafficking of the desmoplakins, desmoglein, and desmocollin to the cell surface; these proteins show a diffuse cytoplasmic distribution and, together with plakoglobin, form detergent-insoluble aggregates [23].
• So far, desmocollin 1, Dsg3, and Dsg1 are known as their target antigens [24].

Analytical, diagnostic and therapeutic context of DSC1

• We elucidated the exon-intron structures of the DSC1 and DSC3 genes using PCR amplification of genomic DNA and direct sequencing of BAC clones [25].
• The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell-cell adhesion [5].
• By immunofluorescence and immunogold EM, Dsc1 labeling was not detected in any suprabasal layer of KOM, but it was present in the upper spinous/granular layers of epidermis [15].
• RT-PCR analysis confirmed that in KOM Dsc1 gene expression was undetectable [15].
• Using Northern blot analyses and ribonuclease protection assays we have found an approximately 5.6 kb mRNA encoding Dsc2 in all the diverse human tissues, tumors and cell lines examined that are known to possess desmosomes, i.e. not only epithelial cells but also myocardiac cells and lymph nodes [26].

References