Desmoglein-2 is a 122.2 kDa
protein composed of 1118
amino acids.[8] Desmoglein-2 is a
calcium-binding
transmembrane glycoprotein component of desmosomes in vertebrate cells. Currently, four desmoglein subfamily members have been identified and all are members of the
cadherincell adhesion molecule superfamily. These desmoglein gene family members are located in a cluster on chromosome 18. This second family member, desmoglein-2 is expressed in
desmosome-containing tissues, such as
cardiac muscle,
colon,
colon carcinoma, and other simple and stratified epithelial-derived cell lines.[6] Desmoglein-2 is the only desmoglein isoform expressed in
cardiomyocytes.
Function
Desmoglein-2 is an integral component of
desmosomes, which are cell-cell junctions between epithelial, myocardial, and certain other cell types. Desmogleins and desmocollins connect extracellularly via homophilic and heterophilic
interactions. The
cytoplasmic tails of desmosomal cadherins bind to
plakoglobin and
plakophilins, which bind
desmoplakin.[9] In
cardiac muscle, desmoglein-2 localizes to the
intercalated disc, responsible for mechanically and electrically coupling adjacent
cardiomyocytes.[10] In vitro studies in HL-1
cardiomyocytes have shown that inhibition of desmoglein-2 binding or mutation of desmoglein-2 protein (
Ala517
Val or
Val920
Gly) at cardiac
intercalated discs results in a reduced strength of cell-cell contact, demonstrating that desmoglein-2 is critical for
cardiomyocyte cohesion.[11]
Studies in transgenic animals have provided insights into desmoglein-2 function. Mice harboring a mutation in DSG-2 in which desmoglein-2 lacked parts of the adhesive extracellular domains were serially examined over time.[12] These mice exhibited white plaque-like lesions in
cardiac muscle as early as 2 weeks, displaying a cardiac phenotype by 4 weeks that involved loss of viable
cardiomyocytes and heavy cell calcification. Other abnormalities included near to complete dissociation of
intercalated discs and
inflammation, and eventual
arrhythmogenic right ventricular cardiomyopathy with
ventricular dilation,
fibrosis and cardiac
arrhythmia. Studies employing another transgenic mutant DSG2 mouse model harboring an
Asn271
Ser showed that this mutation caused widening of
desmosomes and
adherens junctions concomitant with
electrophysiologic abnormalities and enhanced susceptibility to cardiac
arrhythmias.[13] These changes occurred prior to any
cardiomyocytenecrosis or
fibrosis. Additionally, it was demonstrated that desmoglein-2 interacts in vivo with the
sodium channel protein
Na(V)1.5.[13] An additional transgenic model in which desmoglein-2 was knocked out in a cardiac-specific manner showed a loss of adhesive function at
intercalated discs in adult animals, albeit normal heart development. In adulthood, 100% of transgenic mutant mice developed chamber dilation,
necrosis, aseptic
inflammation,
fibrosis and conduction defects, as well as modified distribution of
connexin-43.[14]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Arnemann J, Spurr NK, Magee AI, Buxton RS (Jun 1992). "The human gene (DSG2) coding for HDGC, a second member of the desmoglein subfamily of the desmosomal cadherins, is, like DSG1 coding for desmoglein DGI, assigned to chromosome 18". Genomics. 13 (2): 484–6.
doi:
10.1016/0888-7543(92)90280-6.
PMID1612610.
^Franke WW, Borrmann CM, Grund C, Pieperhoff S (Feb 2006). "The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins". European Journal of Cell Biology. 85 (2): 69–82.
doi:
10.1016/j.ejcb.2005.11.003.
PMID16406610.
^Ozawa M, Terada H, Pedraza C (Nov 1995). "The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein". Journal of Biochemistry. 118 (5): 1077–82.
doi:
10.1093/jb/118.5.1077.
PMID8749329.
Further reading
Koch PJ, Goldschmidt MD, Walsh MJ, Zimbelmann R, Franke WW (Aug 1991). "Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene". European Journal of Cell Biology. 55 (2): 200–8.
PMID1935985.
Simrak D, Cowley CM, Buxton RS, Arnemann J (Jan 1995). "Tandem arrangement of the closely linked desmoglein genes on human chromosome 18". Genomics. 25 (2): 591–4.
doi:
10.1016/0888-7543(95)80067-V.
PMID7790000.
Schäfer S, Koch PJ, Franke WW (Apr 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.
Schäfer S, Stumpp S, Franke WW (May 1996). "Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues". Differentiation; Research in Biological Diversity. 60 (2): 99–108.
doi:
10.1046/j.1432-0436.1996.6020099.x.
PMID8641550.
Ozawa M, Terada H, Pedraza C (Nov 1995). "The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein". Journal of Biochemistry. 118 (5): 1077–82.
doi:
10.1093/jb/118.5.1077.
PMID8749329.
Denning MF, Guy SG, Ellerbroek SM, Norvell SM, Kowalczyk AP, Green KJ (Feb 1998). "The expression of desmoglein isoforms in cultured human keratinocytes is regulated by calcium, serum, and protein kinase C". Experimental Cell Research. 239 (1): 50–9.
doi:
10.1006/excr.1997.3890.
PMID9511724.
Moll I, Houdek P, Schäfer S, Nuber U, Moll R (1999). "Diversity of desmosomal proteins in regenerating epidermis: immunohistochemical study using a human skin organ culture model". Archives of Dermatological Research. 291 (7–8): 437–46.
doi:
10.1007/s004030050435.
PMID10482015.
S2CID6183331.
Zhang H, Li XJ, Martin DB, Aebersold R (Jun 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nature Biotechnology. 21 (6): 660–6.
doi:
10.1038/nbt827.
PMID12754519.
S2CID581283.
Amanchy R, Kalume DE, Iwahori A, Zhong J, Pandey A (2006). "Phosphoproteome analysis of HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC)". Journal of Proteome Research. 4 (5): 1661–71.
doi:
10.1021/pr050134h.
PMID16212419.
Desmoglein-2 is a 122.2 kDa
protein composed of 1118
amino acids.[8] Desmoglein-2 is a
calcium-binding
transmembrane glycoprotein component of desmosomes in vertebrate cells. Currently, four desmoglein subfamily members have been identified and all are members of the
cadherincell adhesion molecule superfamily. These desmoglein gene family members are located in a cluster on chromosome 18. This second family member, desmoglein-2 is expressed in
desmosome-containing tissues, such as
cardiac muscle,
colon,
colon carcinoma, and other simple and stratified epithelial-derived cell lines.[6] Desmoglein-2 is the only desmoglein isoform expressed in
cardiomyocytes.
Function
Desmoglein-2 is an integral component of
desmosomes, which are cell-cell junctions between epithelial, myocardial, and certain other cell types. Desmogleins and desmocollins connect extracellularly via homophilic and heterophilic
interactions. The
cytoplasmic tails of desmosomal cadherins bind to
plakoglobin and
plakophilins, which bind
desmoplakin.[9] In
cardiac muscle, desmoglein-2 localizes to the
intercalated disc, responsible for mechanically and electrically coupling adjacent
cardiomyocytes.[10] In vitro studies in HL-1
cardiomyocytes have shown that inhibition of desmoglein-2 binding or mutation of desmoglein-2 protein (
Ala517
Val or
Val920
Gly) at cardiac
intercalated discs results in a reduced strength of cell-cell contact, demonstrating that desmoglein-2 is critical for
cardiomyocyte cohesion.[11]
Studies in transgenic animals have provided insights into desmoglein-2 function. Mice harboring a mutation in DSG-2 in which desmoglein-2 lacked parts of the adhesive extracellular domains were serially examined over time.[12] These mice exhibited white plaque-like lesions in
cardiac muscle as early as 2 weeks, displaying a cardiac phenotype by 4 weeks that involved loss of viable
cardiomyocytes and heavy cell calcification. Other abnormalities included near to complete dissociation of
intercalated discs and
inflammation, and eventual
arrhythmogenic right ventricular cardiomyopathy with
ventricular dilation,
fibrosis and cardiac
arrhythmia. Studies employing another transgenic mutant DSG2 mouse model harboring an
Asn271
Ser showed that this mutation caused widening of
desmosomes and
adherens junctions concomitant with
electrophysiologic abnormalities and enhanced susceptibility to cardiac
arrhythmias.[13] These changes occurred prior to any
cardiomyocytenecrosis or
fibrosis. Additionally, it was demonstrated that desmoglein-2 interacts in vivo with the
sodium channel protein
Na(V)1.5.[13] An additional transgenic model in which desmoglein-2 was knocked out in a cardiac-specific manner showed a loss of adhesive function at
intercalated discs in adult animals, albeit normal heart development. In adulthood, 100% of transgenic mutant mice developed chamber dilation,
necrosis, aseptic
inflammation,
fibrosis and conduction defects, as well as modified distribution of
connexin-43.[14]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Arnemann J, Spurr NK, Magee AI, Buxton RS (Jun 1992). "The human gene (DSG2) coding for HDGC, a second member of the desmoglein subfamily of the desmosomal cadherins, is, like DSG1 coding for desmoglein DGI, assigned to chromosome 18". Genomics. 13 (2): 484–6.
doi:
10.1016/0888-7543(92)90280-6.
PMID1612610.
^Franke WW, Borrmann CM, Grund C, Pieperhoff S (Feb 2006). "The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins". European Journal of Cell Biology. 85 (2): 69–82.
doi:
10.1016/j.ejcb.2005.11.003.
PMID16406610.
^Ozawa M, Terada H, Pedraza C (Nov 1995). "The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein". Journal of Biochemistry. 118 (5): 1077–82.
doi:
10.1093/jb/118.5.1077.
PMID8749329.
Further reading
Koch PJ, Goldschmidt MD, Walsh MJ, Zimbelmann R, Franke WW (Aug 1991). "Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene". European Journal of Cell Biology. 55 (2): 200–8.
PMID1935985.
Simrak D, Cowley CM, Buxton RS, Arnemann J (Jan 1995). "Tandem arrangement of the closely linked desmoglein genes on human chromosome 18". Genomics. 25 (2): 591–4.
doi:
10.1016/0888-7543(95)80067-V.
PMID7790000.
Schäfer S, Koch PJ, Franke WW (Apr 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.
Schäfer S, Stumpp S, Franke WW (May 1996). "Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues". Differentiation; Research in Biological Diversity. 60 (2): 99–108.
doi:
10.1046/j.1432-0436.1996.6020099.x.
PMID8641550.
Ozawa M, Terada H, Pedraza C (Nov 1995). "The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein". Journal of Biochemistry. 118 (5): 1077–82.
doi:
10.1093/jb/118.5.1077.
PMID8749329.
Denning MF, Guy SG, Ellerbroek SM, Norvell SM, Kowalczyk AP, Green KJ (Feb 1998). "The expression of desmoglein isoforms in cultured human keratinocytes is regulated by calcium, serum, and protein kinase C". Experimental Cell Research. 239 (1): 50–9.
doi:
10.1006/excr.1997.3890.
PMID9511724.
Moll I, Houdek P, Schäfer S, Nuber U, Moll R (1999). "Diversity of desmosomal proteins in regenerating epidermis: immunohistochemical study using a human skin organ culture model". Archives of Dermatological Research. 291 (7–8): 437–46.
doi:
10.1007/s004030050435.
PMID10482015.
S2CID6183331.
Zhang H, Li XJ, Martin DB, Aebersold R (Jun 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nature Biotechnology. 21 (6): 660–6.
doi:
10.1038/nbt827.
PMID12754519.
S2CID581283.
Amanchy R, Kalume DE, Iwahori A, Zhong J, Pandey A (2006). "Phosphoproteome analysis of HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC)". Journal of Proteome Research. 4 (5): 1661–71.
doi:
10.1021/pr050134h.
PMID16212419.