Desmoglein-1 Explained

Desmoglein-1 is a protein that in humans is encoded by the DSG1 gene.^{[1] [2]} Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis.^[3]

Function

Desmosomes are cell-cell junctions between epithelial, myocardial and certain other cell types. Desmoglein-1 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. The protein encoded by this gene has been identified as the autoantigen of the autoimmune skin blistering disease pemphigus foliaceus. It has been found that desmoglein-1 is the target antigen in majority of the cases linked to IgG/IgA pemphigus, which is an autoimmune IgG/IgA antibody mediated response.^[4] Desmoglein-1 is also a target of Staphylococcus exotoxins (exfoliatins) A and B which contribute to the pathoaetiology of staphylococcal scalded skin syndrome (SSSS).

Deficiency of the desmoglein-1 protein has been found to be associated with increased expression of multiple genes encoding allergy-related cytokines.^[5] Desmoglein-1 is haploinsufficient and a mutation in the gene can cause the autosomal dominant mutation striate palmoplantar keratoderma.^[6] In 2013,^[5] cases have arisen where the homozygous loss of the desmoglein-1 gene has resulted in a rare syndrome known as SAM syndrome – severe dermatitis, multiple allergies, and metabolic wasting.^[7]

Interactions

Desmoglein-1 has been shown to interact with PKP3,^[8] PKP2,^[9] and PTPRT (PTPrho)^[10]

See also

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

Further reading

• Amagai M . Desmoglein as a target in autoimmunity and infection . Journal of the American Academy of Dermatology . 48 . 2 . 244–52 . February 2003 . 12582396 . 10.1067/mjd.2003.7 .
• Wheeler GN, Parker AE, Thomas CL, Ataliotis P, Poynter D, Arnemann J, Rutman AJ, Pidsley SC, Watt FM, Rees DA . Desmosomal glycoprotein DGI, a component of intercellular desmosome junctions, is related to the cadherin family of cell adhesion molecules . Proceedings of the National Academy of Sciences of the United States of America . 88 . 11 . 4796–800 . June 1991 . 1711210 . 51753 . 10.1073/pnas.88.11.4796 . 1991PNAS...88.4796W . free .
• 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 .
• Martínez RD . [Characterization of the desmoglein in renal cells in culture] . es . Revista Alergia Mexico . 38 . 2 . 59–64 . 1992 . 1754823 . Characterization of the desmoglein in renal cells in culture .
• Nilles LA, Parry DA, Powers EE, Angst BD, Wagner RM, Green KJ . Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome . Journal of Cell Science . 99 (Pt 4) . 4 . 809–21 . August 1991 . 10.1242/jcs.99.4.809 . 1770008 .
• 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 .
• Simrak D, Cowley CM, Buxton RS, Arnemann J . Tandem arrangement of the closely linked desmoglein genes on human chromosome 18 . Genomics . 25 . 2 . 591–4 . January 1995 . 7790000 . 10.1016/0888-7543(95)80067-V .
• 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 .
• 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) . Pt 1 . 165–74 . January 1998 . 9405290 . 1219028 . 10.1042/bj3290165.
• Marcozzi C, Burdett ID, Buxton RS, Magee AI . Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion . Journal of Cell Science . 111 (Pt 4) . 4 . 495–509 . February 1998 . 10.1242/jcs.111.4.495 . 9443898 .
• Smith EA, Fuchs E . Defining the interactions between intermediate filaments and desmosomes . The Journal of Cell Biology . 141 . 5 . 1229–41 . June 1998 . 9606214 . 2137181 . 10.1083/jcb.141.5.1229 .
• Rickman L, Simrak D, Stevens HP, Hunt DM, King IA, Bryant SP, Eady RA, Leigh IM, Arnemann J, Magee AI, Kelsell DP, Buxton RS . N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma . Human Molecular Genetics . 8 . 6 . 971–6 . June 1999 . 10332028 . 10.1093/hmg/8.6.971 . free .
• Li G, Schaider H, Satyamoorthy K, Hanakawa Y, Hashimoto K, Herlyn M . Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development . Oncogene . 20 . 56 . 8125–35 . December 2001 . 11781826 . 10.1038/sj.onc.1205034 . free .
• Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ . Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling . The Journal of Biological Chemistry . 277 . 12 . 10512–22 . March 2002 . 11790773 . 10.1074/jbc.M108765200 . free .
• Martel P, Gilbert D, Busson M, Loiseau P, Lepage V, Drouot L, Delaporte E, Prost C, Joly P, Charron D, Tron F . Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus . Genes and Immunity . 3 . 4 . 205–10 . June 2002 . 12058255 . 10.1038/sj.gene.6363839 . free .
• Hanakawa Y, Schechter NM, Lin C, Garza L, Li H, Yamaguchi T, Fudaba Y, Nishifuji K, Sugai M, Amagai M, Stanley JR . Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome . The Journal of Clinical Investigation . 110 . 1 . 53–60 . July 2002 . 12093888 . 151035 . 10.1172/JCI15766 .
• 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 .

Notes and References

1. Arnemann J, Spurr NK, Wheeler GN, Parker AE, Buxton RS . Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP) . Genomics . 10 . 3 . 640–5 . July 1991 . 1889810 . 10.1016/0888-7543(91)90446-L .
2. Web site: Entrez Gene: DSG1 desmoglein 1.
3. Book: Beigi, Pooya Khan Mohammad. A Clinician's Guide to Pemphigus Vulgaris. 2018. Springer, Cham. 9783319677583. 3–10. en. 10.1007/978-3-319-67759-0_1. Background.
4. July 2006. Journal der Deutschen Dermatologischen Gesellschaft . 4. 7. 10.1111/ddg.2006.4.issue-7. none. 1610-0379.
5. Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O, Koetsier JL, Gat A, Goldberg I, Bergman R, Spiegel R, Eytan O, Geller S, Peleg S, Shomron N, Goh CS, Wilson NJ, Smith FJ, Pohler E, Simpson MA, McLean WH, Irvine AD, Horowitz M, McGrath JA, Green KJ, Sprecher E . Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting . En . Nature Genetics . 45 . 10 . 1244–1248 . October 2013 . 23974871 . 3791825 . 10.1038/ng.2739 .
6. Has C, Jakob T, He Y, Kiritsi D, Hausser I, Bruckner-Tuderman L . Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies . The British Journal of Dermatology . 172 . 1 . 257–61 . January 2015 . 25041099 . 10.1111/bjd.13247 . 42320016 .
7. McAleer MA, Pohler E, Smith FJ, Wilson NJ, Cole C, MacGowan S, Koetsier JL, Godsel LM, Harmon RM, Gruber R, Crumrine D, Elias PM, McDermott M, Butler K, Broderick A, Sarig O, Sprecher E, Green KJ, McLean WH, Irvine AD . Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin . The Journal of Allergy and Clinical Immunology . 136 . 5 . 1268–76 . November 2015 . 26073755 . 4649901 . 10.1016/j.jaci.2015.05.002 .
8. 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 .
9. Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ . Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling . The Journal of Biological Chemistry . 277 . 12 . 10512–22 . March 2002 . 11790773 . 10.1074/jbc.M108765200 . free .
10. Besco JA, Hooft van Huijsduijnen R, Frostholm A, Rotter A . Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT) . Brain Research . 1116 . 1 . 50–7 . October 2006 . 16973135 . 10.1016/j.brainres.2006.07.122 . 23343123 .