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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Hemidesmosomes


High impact information on Hemidesmosomes


Chemical compound and disease context of Hemidesmosomes


Biological context of Hemidesmosomes


Anatomical context of Hemidesmosomes


Associations of Hemidesmosomes with chemical compounds

  • Upon ligand binding, the alpha6beta4 integrin becomes phosphorylated on tyrosine residues and combines sequentially with the adaptor molecules Shc and Grb2, linking to the ras pathway, and with cytoskeletal elements of hemidesmosomes [21].
  • Expression of chimeric proteins, which consist of the membrane targeting sequence of K-Ras fused to the cytoplasmic domain of BP180 with increasing internal deletions or lacking the NH2 terminus, indicates that the localization of BP180 in hemidesmosomes is mediated by a segment that spans 265 amino acids [22].
  • While alpha 3 beta 1 mediates adhesion, spreading, and migration (Kreidberg, J.A. 2000. Curr. Opin. Cell Biol. 12:548--553), alpha 6 beta 4 is involved in BM anchorage via hemidesmosomes (Borradori, L., and A. Sonnenberg. 1999. J. Invest. Dermatol. 112:411--418) [23].
  • The members of the plakin family of proteins serve as epidermal cytolinkers and components of cell-cell and cell-matrix adhesion complexes, i.e., desmosomes and hemidesmosomes, respectively [24].
  • The alpha6beta4 integrin-a laminin-5 receptor-mediates assembly of hemidesmosomes and recruitment of Shc and phosphoinositide 3-kinase through the unique cytoplasmic extension of beta4 [25].

Gene context of Hemidesmosomes

  • We suggest that CD151 plays a role in the formation and stability of hemidesmosomes by providing a framework for the spatial organization of the different hemidesmosomal components [12].
  • These observations suggest that the EGF-R causes disassembly of hemidesmosomes by activating Fyn, which in turn phosphorylates the beta4 cytoplasmic domain [19].
  • Others, such as CD9 and CD81, remain diffusely distributed at the cell surface.In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin alpha6beta4 [12].
  • Elongation of the epidermis of the nematode Caenorhabditis elegans involves both actomyosin-mediated changes in lateral epidermal cell shape and body muscle attachment to dorsal and ventral epidermal cells via intermediate-filament/hemidesmosome structures. vab-19 mutants are defective in epidermal elongation and muscle attachment to the epidermis [26].
  • We propose that the BP230 N terminus competes with endogenous BP230 protein for BP180 binding and inhibits incorporation of BP180 into the cell surface at the site of the hemidesmosome [27].

Analytical, diagnostic and therapeutic context of Hemidesmosomes


  1. Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolocalization of this protein to the hemidesmosome. Diaz, L.A., Ratrie, H., Saunders, W.S., Futamura, S., Squiquera, H.L., Anhalt, G.J., Giudice, G.J. J. Clin. Invest. (1990) [Pubmed]
  2. Gene correction of integrin beta4-dependent pyloric atresia-junctional epidermolysis bullosa keratinocytes establishes a role for beta4 tyrosines 1422 and 1440 in hemidesmosome assembly. Dellambra, E., Prislei, S., Salvati, A.L., Madeddu, M.L., Golisano, O., Siviero, E., Bondanza, S., Cicuzza, S., Orecchia, A., Giancotti, F.G., Zambruno, G., De Luca, M. J. Biol. Chem. (2001) [Pubmed]
  3. Hemidesmosomes show abnormal association with the keratin filament network in junctional forms of epidermolysis bullosa. McMillan, J.R., McGrath, J.A., Tidman, M.J., Eady, R.A. J. Invest. Dermatol. (1998) [Pubmed]
  4. Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies. Zillikens, D., Rose, P.A., Balding, S.D., Liu, Z., Olague-Marchan, M., Diaz, L.A., Giudice, G.J. J. Invest. Dermatol. (1997) [Pubmed]
  5. Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris. Joly, P., Thomine, E., Gilbert, D., Verdier, S., Delpech, A., Prost, C., Lebbe, C., Lauret, P., Tron, F. J. Invest. Dermatol. (1994) [Pubmed]
  6. Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice. van der Neut, R., Krimpenfort, P., Calafat, J., Niessen, C.M., Sonnenberg, A. Nat. Genet. (1996) [Pubmed]
  7. Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice. Georges-Labouesse, E., Messaddeq, N., Yehia, G., Cadalbert, L., Dierich, A., Le Meur, M. Nat. Genet. (1996) [Pubmed]
  8. Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Carter, W.G., Ryan, M.C., Gahr, P.J. Cell (1991) [Pubmed]
  9. Novel ITGB4 mutations in a patient with junctional epidermolysis bullosa-pyloric atresia syndrome and altered basement membrane zone immunofluorescence for the alpha6beta4 integrin. Takizawa, Y., Shimizu, H., Nishikawa, T., Hatta, N., Pulkkinen, L., Uitto, J. J. Invest. Dermatol. (1997) [Pubmed]
  10. Acquired skin disease of hemidesmosomes. Zillikens, D. J. Dermatol. Sci. (1999) [Pubmed]
  11. Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. Dowling, J., Yu, Q.C., Fuchs, E. J. Cell Biol. (1996) [Pubmed]
  12. The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes. Sterk, L.M., Geuijen, C.A., Oomen, L.C., Calafat, J., Janssen, H., Sonnenberg, A. J. Cell Biol. (2000) [Pubmed]
  13. Protein kinase C-alpha phosphorylation of specific serines in the connecting segment of the beta 4 integrin regulates the dynamics of type II hemidesmosomes. Rabinovitz, I., Tsomo, L., Mercurio, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  14. Characterization of mice lacking the tetraspanin superfamily member CD151. Wright, M.D., Geary, S.M., Fitter, S., Moseley, G.W., Lau, L.M., Sheng, K.C., Apostolopoulos, V., Stanley, E.G., Jackson, D.E., Ashman, L.K. Mol. Cell. Biol. (2004) [Pubmed]
  15. Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Frye, M., Gardner, C., Li, E.R., Arnold, I., Watt, F.M. Development (2003) [Pubmed]
  16. Differential formation of desmosomes and hemidesmosomes in epidermal cell cultures treated with retinoic acid. Christophers, E., Wolff, H.H. Nature (1975) [Pubmed]
  17. The internal affairs of an integrin. Quaranta, V., Jones, J.C. Trends Cell Biol. (1991) [Pubmed]
  18. Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease. Domloge-Hultsch, N., Gammon, W.R., Briggaman, R.A., Gil, S.G., Carter, W.G., Yancey, K.B. J. Clin. Invest. (1992) [Pubmed]
  19. EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. Mariotti, A., Kedeshian, P.A., Dans, M., Curatola, A.M., Gagnoux-Palacios, L., Giancotti, F.G. J. Cell Biol. (2001) [Pubmed]
  20. The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. Rabinovitz, I., Mercurio, A.M. J. Cell Biol. (1997) [Pubmed]
  21. The intracellular functions of alpha6beta4 integrin are regulated by EGF. Mainiero, F., Pepe, A., Yeon, M., Ren, Y., Giancotti, F.G. J. Cell Biol. (1996) [Pubmed]
  22. The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit. Borradori, L., Koch, P.J., Niessen, C.M., Erkeland, S., van Leusden, M.R., Sonnenberg, A. J. Cell Biol. (1997) [Pubmed]
  23. Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin. Hintermann, E., Bilban, M., Sharabi, A., Quaranta, V. J. Cell Biol. (2001) [Pubmed]
  24. Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development. Aho, S., Li, K., Ryoo, Y., McGee, C., Ishida-Yamamoto, A., Uitto, J., Klement, J.F. Mol. Cell. Biol. (2004) [Pubmed]
  25. Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5-dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB, causing defects in epidermal growth and migration. Nikolopoulos, S.N., Blaikie, P., Yoshioka, T., Guo, W., Puri, C., Tacchetti, C., Giancotti, F.G. Mol. Cell. Biol. (2005) [Pubmed]
  26. C. elegans ankyrin repeat protein VAB-19 is a component of epidermal attachment structures and is essential for epidermal morphogenesis. Ding, M., Goncharov, A., Jin, Y., Chisholm, A.D. Development (2003) [Pubmed]
  27. The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome. Hopkinson, S.B., Jones, J.C. Mol. Biol. Cell (2000) [Pubmed]
  28. Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes. Stepp, M.A., Spurr-Michaud, S., Tisdale, A., Elwell, J., Gipson, I.K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  29. A dynamic podosome-like structure of epithelial cells. Spinardi, L., Rietdorf, J., Nitsch, L., Bono, M., Tacchetti, C., Way, M., Marchisio, P.C. Exp. Cell Res. (2004) [Pubmed]
  30. Thermolysin treatment: a new method for dermo-epidermal separation. Walzer, C., Benathan, M., Frenk, E. J. Invest. Dermatol. (1989) [Pubmed]
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