Desmoglein-3 Explained

Desmoglein-3 is a protein that in humans is encoded by the DSG3 gene.^{[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]

Function

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. 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.

Interactions

Desmoglein 3 has been shown to interact with PKP3.^[7]

See also

• Desmoglein
• List of target antigens in pemphigus
• List of conditions caused by problems with junctional proteins

Further reading

• Amagai M, Klaus-Kovtun V, Stanley JR . Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion . Cell . 67 . 5 . 869–77 . November 1991 . 1720352 . 10.1016/0092-8674(91)90360-B . 21647774 .
• Roh JY, Stanley JR . 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 . May 1995 . 7738346 . 10.1111/1523-1747.ep12606963 . free .
• Wang Y, Amagai M, Minoshima S, Sakai K, Green KJ, Nishikawa T, Shimizu N . The human genes for desmogleins (DSG1 and DSG3) are located in a small region on chromosome 18q12 . Genomics . 20 . 3 . 492–5 . April 1994 . 8034325 . 10.1006/geno.1994.1207 .
• Schäfer S, Koch PJ, Franke WW . 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 . April 1994 . 8143788 . 10.1006/excr.1994.1103 .
• Kárpáti S, Amagai M, Prussick R, Cehrs K, Stanley JR . Pemphigus vulgaris antigen, a desmoglein type of cadherin, is localized within keratinocyte desmosomes . The Journal of Cell Biology . 122 . 2 . 409–15 . July 1993 . 8320263 . 2119642 . 10.1083/jcb.122.2.409 .
• Silos SA, Tamai K, Li K, Kivirikko S, Kouba D, Christiano AM, Uitto J . 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 . July 1996 . 8663392 . 10.1074/jbc.271.29.17504 . free .
• Marsden MD, Collins JE, Greenwood MD, Adams MJ, Fleming TP, Magee AI, Buxton RS . Cloning and transcriptional analysis of the promoter of the human type 2 desmocollin gene (DSC2) . Gene . 186 . 2 . 237–47 . February 1997 . 9074502 . 10.1016/S0378-1119(96)00715-9 .
• Adams MJ, Reichel MB, King IA, Marsden MD, Greenwood MD, Thirlwell H, Arnemann J, Buxton RS, Ali RR . Characterization of the regulatory regions in the human desmoglein genes encoding the pemphigus foliaceous and pemphigus vulgaris antigens . The Biochemical Journal . 329 (Pt 1) . 165–74 . January 1998 . 9405290 . 1219028 . 10.1042/bj3290165. 329 . Pt 1 .
• Shirakata Y, Amagai M, Hanakawa Y, Nishikawa T, Hashimoto K . 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 . January 1998 . 9424092 . 10.1046/j.1523-1747.1998.00085.x . free .
• Amagai M, Nishikawa T, Nousari HC, Anhalt GJ, Hashimoto T . Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice . The Journal of Clinical Investigation . 102 . 4 . 775–82 . August 1998 . 9710446 . 508940 . 10.1172/JCI3647 .
• Ishikawa H, Li K, Tamai K, Sawamura D, Uitto J . Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily . Experimental Dermatology . 9 . 4 . 229–39 . August 2000 . 10949543 . 10.1034/j.1600-0625.2000.009004229.x . 30935336 .
• Czerwenka KF, Manavi M, Hosmann J, Jelincic D, Pischinger KI, Battistutti WB, Behnam M, Kubista E . Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue . Cancer Detection and Prevention . 25 . 3 . 268–79 . 2001 . 11425269 .
• Weiske J, Schöneberg T, Schröder W, Hatzfeld M, Tauber R, Huber O . The fate of desmosomal proteins in apoptotic cells . The Journal of Biological Chemistry . 276 . 44 . 41175–81 . November 2001 . 11500511 . 10.1074/jbc.M105769200 . free .
• Andl CD, Stanley JR . Central role of the plakoglobin-binding domain for desmoglein 3 incorporation into desmosomes . The Journal of Investigative Dermatology . 117 . 5 . 1068–74 . November 2001 . 11710914 . 10.1046/j.0022-202x.2001.01528.x . free .
• Merritt AJ, Berika MY, Zhai W, Kirk SE, Ji B, Hardman MJ, Garrod DR . Suprabasal desmoglein 3 expression in the epidermis of transgenic mice results in hyperproliferation and abnormal differentiation . Molecular and Cellular Biology . 22 . 16 . 5846–58 . August 2002 . 12138195 . 133994 . 10.1128/MCB.22.16.5846-5858.2002 .
• Hanakawa Y, Amagai M, Shirakata Y, Yahata Y, Tokumaru S, Yamasaki K, Tohyama M, Sayama K, Hashimoto K . Differential effects of desmoglein 1 and desmoglein 3 on desmosome formation . The Journal of Investigative Dermatology . 119 . 6 . 1231–6 . December 2002 . 12485422 . 10.1046/j.1523-1747.2002.19648.x . free .
• Veldman C, Stauber A, Wassmuth R, Uter W, Schuler G, Hertl M . 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 . January 2003 . 12496453 . 10.4049/jimmunol.170.1.635 . free .
• Posthaus H, Dubois CM, Müller E . Novel insights into cadherin processing by subtilisin-like convertases . FEBS Letters . 536 . 1–3 . 203–8 . February 2003 . 12586364 . 10.1016/S0014-5793(02)03897-8 . 26668652 . free .

Notes and References

1. Arnemann J, Spurr NK, Buxton RS . 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 . May 1992 . 1601426 . 10.1007/bf00220557 . 30558450 .
2. Web site: Entrez Gene: DSG3 desmoglein 3 (pemphigus vulgaris antigen).
3. Book: Beigi, Pooya Khan Mohammad . A Clinician's Guide to Pemphigus Vulgaris. 2018. Springer, Cham. 9783319677583. 3–10. 10.1007/978-3-319-67759-0_1.
4. Hartlieb E, Kempf B, Partilla M, Vigh B, Spindler V, Waschke J . Desmoglein 2 is less important than desmoglein 3 for keratinocyte cohesion . PLOS ONE . 8 . 1 . e53739 . 2013-01-11 . 23326495 . 3543261 . 10.1371/journal.pone.0053739 . 2013PLoSO...853739H . free .
5. Fang WK, Gu W, Liao LD, Chen B, Wu ZY, Wu JY, Shen J, Xu LY, Li EM . Prognostic significance of desmoglein 2 and desmoglein 3 in esophageal squamous cell carcinoma . Asian Pacific Journal of Cancer Prevention . 15 . 2 . 871–6 . 2014 . 24568510 . 10.7314/apjcp.2014.15.2.871 . free .
6. Spindler V, Rötzer V, Dehner C, Kempf B, Gliem M, Radeva M, Hartlieb E, Harms GS, Schmidt E, Waschke J . Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering . The Journal of Clinical Investigation . 123 . 2 . 800–11 . February 2013 . 23298835 . 3561799 . 10.1172/jci60139 .
7. Bonné S, Gilbert B, Hatzfeld M, Chen X, Green KJ, van Roy F . Defining desmosomal plakophilin-3 interactions . The Journal of Cell Biology . 161 . 2 . 403–16 . April 2003 . 12707304 . 2172904 . 10.1083/jcb.200303036 . 1854/LU-210987 .