Desmoglein-3 (Dsg3), a member of the cadherin superfamily, serves as an adhesion protein in desmosomes and is crucial in the maintenance of epithelial integrity [1]. Recent evidence suggests that Dsg3 acts as a regulator of various pathways governing cell adhesion, proliferation, differentiation, morphogenesis, and migration [2]. Although this requires further investigation, findings provide the first evidence that Dsg3 may play a role in regulating the Rab protein expression [3]. Dsg3 is required for the peripheral recruitment of proteins following calcium-induced junction formation, indicating its importance in cell adhesion [4]. Moreover, hypomorphic Dsg3 protein expression may support intercellular adhesion and prevent spontaneous acantholysis, but it appears insufficient to prevent epithelial sloughing and lesions resulting from mechanical damage or stresses [5]. Dsg3, along with Dsg1, mediates cell-cell adhesion in the epidermis and mucous membranes [6]. Furthermore, Dsg3 is a component of desmosomes and its endocytosis and reduction in protein levels can exacerbate the effects of pemphigus vulgaris antibodies on its adhesive function at the cell surface [7]. Dsg3 is proposed to compensate for the loss of Dsg3-mediated adhesion function in Dsg3 knockout mice, suggesting its compensatory role [8]. Additionally, Dsg3's ability to activate various signal pathways, including tyrosine protein kinase Src and the Fos-binding protein c-Jun, regulates the actin and actomyosin cytoskeleton [9].
References:
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[2] A. Rehman, Y. Cai, C. Hünefeld, H. Jedličková, Y. Huang, M. Tehet al., "The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53", Cell Death and Disease, vol. 10, no. 10, 2019. https://doi.org/10.1038/s41419-019-1988-0
[3] H. Moftah, K. Dias, E. Apu, L. Liu, J. Uttagomol, L. Bergmeieret al., "Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion", Cell Adhesion & Migration, vol. 11, no. 3, p. 211-232, 2016. https://doi.org/10.1080/19336918.2016.1195942
[4] S. Tsang, L. Brown, K. Lin, L. Liu, K. Piper, E. O’Tooleet al., "Non‐junctional human desmoglein 3 acts as an upstream regulator of src in e‐cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris", The Journal of Pathology, vol. 227, no. 1, p. 81-93, 2012. https://doi.org/10.1002/path.3982
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[6] C. Hammers and J. Wrammert, "The pemphigus monoclonal antibody clone p5g6 (ax353) retains cell-surface staining by immunofluorescence and desmoglein binding by elisa in an engineered scfv-fc format", Antibody Reports, vol. 5, no. 1, p. e756, 2022. https://doi.org/10.24450/journals/abrep.2022.e756
[7] C. Calkins, S. Setzer, J. Jennings, S. Summers, K. Tsunoda, M. Amagaiet al., "Desmoglein endocytosis and desmosome disassembly are coordinated responses to pemphigus autoantibodies", Journal of Biological Chemistry, vol. 281, no. 11, p. 7623-7634, 2006. https://doi.org/10.1074/jbc.m512447200
[8] C. Yj, C. Jt, L. L, W. Hm, L. Ct, C. Chiuet al., "Dsg3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis", Oncogene, vol. 26, no. 3, p. 467-476, 2006. https://doi.org/10.1038/sj.onc.1209802
[9] J. Uttagomol, U. Ahmad, A. Rehman, Y. Huang, A. Laly, A. Kanget al., "Evidence for the desmosomal cadherin desmoglein-3 in regulating yap and phospho-yap in keratinocyte responses to mechanical forces", International Journal of Molecular Sciences, vol. 20, no. 24, p. 6221, 2019. https://doi.org/10.3390/ijms20246221
