Focal adhesions in the skin: lessons learned from skin fragility disorders

European Journal of Dermatology - Tập 27 - Trang 8-11 - 2017
Cristina Has1,2, Yinghong He1,2
1Department of Dermatology, Medical Center – University of Freiburg, Freiburg, Germany
2Faculty of Medicine, University of Freiburg, Freiburg, Germany

Tóm tắt

Focal adhesions are large multiprotein cell-matrix adhesion complexes, which regulate multiple cellular functions, such as adhesion and migration. Their biological significance in skin is underscored by two genetic disorders, the Kindler syndrome and the interstitial lung disease, nephrotic syndrome and epidermolysis bullosa, in which mutations affect focal adhesion proteins, kindlin-1 and the integrin α3 subunit, respectively. Here we provide an overview of what we learned from the study of the molecular mechanisms of these diseases. Emphasis is put on the point of view of the clinician dermatologist.

Tài liệu tham khảo

Schiller HB, Friedel CC, Boulegue C, Fassler R. Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins. EMBO Rep 2011; 12: 259–66. Horton ER, Byron A, Askari JA, et al. Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly. Nat Cell Biol 2015; 17: 1577–87. Ajeian JN, Horton ER, Astudillo P, et al. Proteomic analysis of integrin-associated complexes from mesenchymal stem cells. Proteomic Clin Appl 2016; 10: 51–7. Winograd-Katz SE, Fässler R, Geiger B, Legate KR. The integrin adhesome: from genes and proteins to human disease. Nat Rev Mol Cell Biol 2014; 15: 273–88. Manninen A, Varjosalo M. A proteomics view on integrin-mediated adhesions. Proteomics 2017; 17: 920–9. Has C, Nyström A. Epidermal basement membrane in health and disease. Curr Top Membr 2015; 76: 117–70. Has C, Bruckner-Tuderman L. The genetics of skin fragility. Annu Rev Genomics Hum Genet 2014; 15: 245–68. Jobard F, Bouadjar B, Caux F, et al. Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome. Hum Mol Genet 2003; 12: 925–35. Siegel DH, Ashton GH, Penagos HG, et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellularmatrix linker protein UNC-112, causes Kindler syndrome. Am J Hum Genet 2003; 73: 174–87. Mackinnon AC, Qadota H, Norman KR, Moerman DG,Williams BD. C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes. Curr Biol 2002; 12: 787–97. Has C, Spartà G, Kiritsi D, et al. Integrin α3 mutations with kidney, lung, and skin disease. N Engl J Med 2012; 366: 1508–14. Nicolaou N, Margadant C, Kevelam SH, et al. Gain of glycosylation in integrin alpha3 causes lung disease and nephrotic syndrome. J Clin Invest 2012; 122: 4375–87. He Y, Esser P, Heinemann A, Bruckner-Tuderman L, Has C. Kindlin-1 and -2 have overlapping functions in epithelial cells implications for phenotype modification. Am J Pathol 2011; 178: 975–82. Bandyopadhyay A, Rothschild G, Kim S, Calderwood DA, Raghavan S. Functional differences between kindlin-1 and kindlin-2 in keratinocytes. J Cell Sci 2012; 125: 2172–84. Fine J-D, Bruckner-Tuderman L, Eady RAJ, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014; 70: 1103–26. Has C, Castiglia D, del Rio M, et al. Kindler syndrome: extension of FERMT1 mutational spectrum and natural history. Hum Mutat 2011; 32: 1204–12. Zhang X, Luo S, Wu J, et al. KIND1 loss sensitizes keratinocytes to UV-induced inflammatory response and DNA damage. J Invest Dermatol 2017; 137: 475–83. Maier K, He Y, Esser PR, et al. Single amino acid deletion in kindlin-1 results in partial protein degradation which can be rescued by chaperone treatment. J Invest Dermatol 2016; 136: 920–9. Maier K, He Y, Wölfle U, et al. UV-B-induced cutaneous inflammation and prospects for antioxidant treatment in Kindler syndrome. Hum Mol Genet 2016; 25: 5339–52. Rognoni E, Widmaier M, Jakobson M, et al. Kindlin-1 controls Wnt and TGF-availability to regulate cutaneous stem cell proliferation. Nat Med 2014; 20: 350–9. Patel H, Zich J, Serrels B, et al. Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1. Nat Commun 2013; 4: 2056. Patel H, Stavrou I, Shrestha RL, Draviam V, Frame MC, Brunton VG. Kindlin1 regulates microtubule function to ensure normal mitosis. J Mol Cell Biol 2016; 8: 338–48. Yalcin EG, He Y, Orhan D, Pazzagli C, Emiralioglu N, Has C. Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. Hum Mol Genet 2015; 24: 3679–88. Yamada M, Sekiguchi K. Disease-associated single amino acid mutation in the calf-1 domain of integrin alpha3 leads to defects in its processing and cell surface expression. Biochem Biophys Res Commun 2013; 441: 988–93. Pazzagli C, He Y, Busch H, et al. Absence of the integrin α3 subunit induces an activated phenotype in human keratinocytes. J Invest Dermatol 2017, Feb 3. pii: S0022-202X(17)30109-4. doi: 10.1016/j.jid.2017.01.018. [Epub ahead of print].