Desmoglein-3 is a protein that in humans is encoded by the DSG3gene.[1][2] In the skin epidermis Desmoglein-3 is expressed in the basal lower layers of the epidermis, and dominates in terms of expression on mucosal surfaces compared to Desmoglein-1.[3]
Desmosomes are cell-cell junctions between epithelial, myocardial, and certain other cell types. Desmoglein 3 is a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells. Currently, four desmoglein subfamily members have been identified and all are members of the cadherin cell adhesion molecule superfamily. These desmoglein gene family members are located in a cluster on chromosome 18. This protein, along with Desmoglein-1, has been identified as the autoantigen of the autoimmune skin blistering disease pemphigus vulgaris.[4] The mucosal dominant form of pemphigus vulgaris only involves antibodies against Desmoglein-3 and causes mucosal erosions, but no skin lesions.[3] Desmoglein-3 serves as a prognostic marker of Esophageal Squamous Cell Carcinoma (ESCC), and may even be involved in the progression of ESCC.[5]
Pathogenicity
Pathogenicity of Desmoglein-3 antibodies comes from the existence of a tryptophan residue that could be interacting with the binding pocket that is necessary for trans-interaction of Desmoglein molecules.[6] Such antibodies can lead to the cause of skin disorders like pemphigus vulgaris.
↑Arnemann J, Spurr NK, Buxton RS (May 1992). "The human gene (DSG3) coding for the pemphigus vulgaris antigen is, like the genes coding for the other two known desmogleins, assigned to chromosome 18". Human Genetics. 89 (3): 347–50. doi:10.1007/bf00220557. PMID1601426.
↑Hartlieb E, Kempf B, Partilla M, Vigh B, Spindler V, Waschke J (2013-01-11). "Desmoglein 2 is less important than desmoglein 3 for keratinocyte cohesion". PLOS One. 8 (1): e53739. doi:10.1371/journal.pone.0053739. PMID23326495.
↑Fang WK, Gu W, Liao LD, Chen B, Wu ZY, Wu JY, Shen J, Xu LY, Li EM (2014). "Prognostic significance of desmoglein 2 and desmoglein 3 in esophageal squamous cell carcinoma". Asian Pacific Journal of Cancer Prevention : APJCP. 15 (2): 871–6. doi:10.7314/apjcp.2014.15.2.871. PMID24568510.
Amagai M, Klaus-Kovtun V, Stanley JR (November 1991). "Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion". Cell. 67 (5): 869–77. doi:10.1016/0092-8674(91)90360-B. PMID1720352.
Roh JY, Stanley JR (May 1995). "Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes requires the cadherin-like intracytoplasmic segment". The Journal of Investigative Dermatology. 104 (5): 720–4. doi:10.1111/1523-1747.ep12606963. PMID7738346.
Wang Y, Amagai M, Minoshima S, Sakai K, Green KJ, Nishikawa T, Shimizu N (April 1994). "The human genes for desmogleins (DSG1 and DSG3) are located in a small region on chromosome 18q12". Genomics. 20 (3): 492–5. doi:10.1006/geno.1994.1207. PMID8034325.
Schäfer S, Koch PJ, Franke WW (April 1994). "Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins". Experimental Cell Research. 211 (2): 391–9. doi:10.1006/excr.1994.1103. PMID8143788.
Silos SA, Tamai K, Li K, Kivirikko S, Kouba D, Christiano AM, Uitto J (July 1996). "Cloning of the gene for human pemphigus vulgaris antigen (desmoglein 3), a desmosomal cadherin. Characterization of the promoter region and identification of a keratinocyte-specific cis-element". The Journal of Biological Chemistry. 271 (29): 17504–11. doi:10.1074/jbc.271.29.17504. PMID8663392.
Marsden MD, Collins JE, Greenwood MD, Adams MJ, Fleming TP, Magee AI, Buxton RS (February 1997). "Cloning and transcriptional analysis of the promoter of the human type 2 desmocollin gene (DSC2)". Gene. 186 (2): 237–47. doi:10.1016/S0378-1119(96)00715-9. PMID9074502.
Shirakata Y, Amagai M, Hanakawa Y, Nishikawa T, Hashimoto K (January 1998). "Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1". The Journal of Investigative Dermatology. 110 (1): 76–8. doi:10.1046/j.1523-1747.1998.00085.x. PMID9424092.
Ishikawa H, Li K, Tamai K, Sawamura D, Uitto J (August 2000). "Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily". Experimental Dermatology. 9 (4): 229–39. doi:10.1034/j.1600-0625.2000.009004229.x. PMID10949543.
Czerwenka KF, Manavi M, Hosmann J, Jelincic D, Pischinger KI, Battistutti WB, Behnam M, Kubista E (2001). "Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue". Cancer Detection and Prevention. 25 (3): 268–79. PMID11425269.
Weiske J, Schöneberg T, Schröder W, Hatzfeld M, Tauber R, Huber O (November 2001). "The fate of desmosomal proteins in apoptotic cells". The Journal of Biological Chemistry. 276 (44): 41175–81. doi:10.1074/jbc.M105769200. PMID11500511.
Andl CD, Stanley JR (November 2001). "Central role of the plakoglobin-binding domain for desmoglein 3 incorporation into desmosomes". The Journal of Investigative Dermatology. 117 (5): 1068–74. doi:10.1046/j.0022-202x.2001.01528.x. PMID11710914.
Hanakawa Y, Amagai M, Shirakata Y, Yahata Y, Tokumaru S, Yamasaki K, Tohyama M, Sayama K, Hashimoto K (December 2002). "Differential effects of desmoglein 1 and desmoglein 3 on desmosome formation". The Journal of Investigative Dermatology. 119 (6): 1231–6. doi:10.1046/j.1523-1747.2002.19648.x. PMID12485422.
Veldman C, Stauber A, Wassmuth R, Uter W, Schuler G, Hertl M (January 2003). "Dichotomy of autoreactive Th1 and Th2 cell responses to desmoglein 3 in patients with pemphigus vulgaris (PV) and healthy carriers of PV-associated HLA class II alleles". Journal of Immunology. 170 (1): 635–42. doi:10.4049/jimmunol.170.1.635. PMID12496453.
Posthaus H, Dubois CM, Müller E (February 2003). "Novel insights into cadherin processing by subtilisin-like convertases". FEBS Letters. 536 (1–3): 203–8. doi:10.1016/S0014-5793(02)03897-8. PMID12586364.
