Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The biology and regulation of corneodesmosomes

  • 1274 Accesses

  • 20 Citations


The stratum corneum of the epidermis is composed of stacked dead corneocytes embedded in lipid layers and is the main protective shield of the skin. The thickness of the stratum corneum is maintained fairly constantly through the balance between new cell creation and old cell removal. Corneodesmosomes are the main intercellular adhesive structures in the stratum corneum. They are transformed from desmosomes at the most superficial layer of the stratum granulosum of the epidermis. The major compositional distinction from desmosomes is the presence of corneodesmosin in the extracellular portion. Furthermore, corneodesmosomes are structurally different from desmosomes in that (1) they do not have a tri-lamellar desmoglea but rather one that is homogeneously electron-dense and (2) attachment plaques are integrated into a part of the cornified cell envelopes. When the extracellular regions of corneodesmosomes are fully degraded, desquamation occurs. The degradation process of corneodesmosomes is carefully controlled by a number of proteases and their inhibitors. The most important proteases involved in this process are the kallikrein-related peptidases. Their main inhibitor is the lympho-epithelial Kazal-type related inhibitor. Other regulators of this process include matriptase, meprin and mesotrypsin.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. Beaufort N, Plaza K, Utzschneider D, Schwarz A, Burkhart JM, Creutzburg S, Debela M, Schmitt M, Ries C, Magdolen V (2010) Interdependence of kallikrein-related peptidases in proteolytic networks. Biol Chem 391:581–587

  2. Bernard D, Mehul B, Thomas-Collignon A, Simonetti L, Remy V, Bernard MA, Schmidt R (2003) Analysis of proteins with caseinolytic activity in a human stratum corneum extract revealed a yet unidentified cysteine protease and identified the so-called "stratum corneum thiol protease" as cathepsin L2. J Invest Dermatol 120:592–600

  3. Borgono CA, Michael IP, Komatsu N, Jayakumar A, Kapadia R, Clayman GL, Sotiropoulou G, Diamandis EP (2007) A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J Biol Chem 282:3640–3652

  4. Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T (2005) A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol 124:198–203

  5. Brattsand M, Stefansson K, Hubiche T, Nilsson SK, Egelrud T (2009) SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor. J Invest Dermatol 129:1656–1665

  6. Caubet C, Jonca N, Brattsand M, Guerrin M, Bernard D, Schmidt R, Egelrud T, Simon M, Serre G (2004) Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J Invest Dermatol 122:1235–1244

  7. Chapman SJ, Walsh A (1990) Desmosomes, corneosomes and desquamation. An ultrastructural study of adult pig epidermis. Arch Dermatol Res 282:304–310

  8. Debela M, Goettig P, Magdolen V, Huber R, Schechter NM, Bode W (2007a) Structural basis of the zinc inhibition of human tissue kallikrein 5. J Mol Biol 373:1017–1031

  9. Debela M, Hess P, Magdolen V, Schechter NM, Steiner T, Huber R, Bode W, Goettig P (2007b) Chymotryptic specificity determinants in the 1.0 Å structure of the zinc-inhibited human tissue kallikrein 7. Proc Natl Acad Sci U S A 104:16086–16091

  10. Deraison C, Bonnart C, Lopez F, Besson C, Robinson R, Jayakumar A, Wagberg F, Brattsand M, Hachem JP, Leonardsson G, Hovnanian A (2007) LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell 18:3607–3619

  11. Elias PM, Crumrine D, Rassner U, Hachem JP, Menon GK, Man W, Choy MH, Leypoldt L, Feingold KR, Williams ML (2004) Basis for abnormal desquamation and permeability barrier dysfunction in RXLI. J Invest Dermatol 122:314–319

  12. Fischer J, Meyer-Hoffert U (2013) Regulation of kallikrein-related peptidases in the skin—from physiology to diseases to therapeutic options. Thromb Haemost 110:442–449

  13. Fischer J, Koblyakova Y, Latendorf T, Wu Z, Meyer-Hoffert U (2013) Cross-linking of SPINK6 by transglutaminases protects from epidermal proteases. J Invest Dermatol 133:1170–1177

  14. Franzke C-W, Baici A, Bartels J, Christophers E, Wiedow O (1996) Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation. J Biol Chem 271:1886-1890

  15. Galliano MF, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M (2006) A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. J Biol Chem 281:5780–5789

  16. Haftek M, Callejon S, Sandjeu Y, Padois K, Falson F, Pirot F, Portes P, Demarne F, Jannin V (2011) Compartmentalization of the human stratum corneum by persistent tight junction-like structures. Exp Dermatol 20:617–621

  17. Heiker JT, Klöting N, Kovacs P, Kuettner EB, Sträter N, Schultz S, Kern M, Stumvoll M, Blüher M, Beck-Sickinger AG (2013) Vaspin inhibits kallikrein 7 by serpin mechanism. Cell Mol Life Sci 70:2569–2583

  18. Horikoshi I, Uchiwa B (1999) Role of endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation. Br J Dermatol 141:453–459

  19. Igarashi S, Takizawa T, Yasuda Y, Uchiwa H, Hayashi S, Brysk H, Robinson JM, Yamamoto K, Brysk MM, Horikoshi T (2004) Cathepsin D, but not cathepsin E, degrades desmosomes during epidermal desquamation. Br J Dermatol 151:355–361

  20. Igawa S, Kishibe M, Murakami M, Honma M, Takahashi H, Iizuka H, Ishida-Yamamoto A (2011) Tight junctions in the stratum corneum explain spatial differences in corneodesmosome degradation. Exp Dermatol 20:53–57

  21. Ishida-Yamamoto A, Igawa S (2014) Genetic skin diseases related to desmosomes and corneodesmosomes. J Dermatol Sci 74:99–105

  22. Ishida-Yamamoto A, Eady RA, Watt FM, Roop DR, Hohl D, Iizuka H (1996) Immunoelectron microscopic analysis of cornified cell envelope formation in normal and psoriatic epidermis. J Histochem Cytochem 44:167–175

  23. Ishida-Yamamoto A, Deraison C, Bonnart C, Bitoun E, Robinson R, O'Brien TJ, Wakamatsu K, Ohtsubo S, Takahashi H, Hashimoto Y, Dopping-Hepenstal PJ, McGrath JA, Iizuka H, Richard G, Hovnanian A (2005) LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. J Invest Dermatol 124:360–366

  24. Ishida-Yamamoto A, Igawa S, Kishibe M (2011) Order and disorder in corneocyte adhesion. J Dermatol 38:645–654

  25. Ishida-Yamamoto A, Kishibe M, Murakami M, Honma M, Takahashi H, Iizuka H (2012) Lamellar granule secretion starts before the establishment of tight junction barrier for paracellular tracers in mammalian epidermis. PLoS One 7:e31641

  26. Jonca N, Leclerc EA, Caubet C, Simon M, Guerrin M, Serre G (2011) Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses. Eur J Dermatol 21 (Suppl 2):35–42

  27. Kantyka T, Fischer J, Wu Z, Declercq W, Reiss K, Schröder JM, Meyer-Hoffert U (2011) Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6. Peptides 32:1187–1192

  28. List K, Haudenschild CC, Szabo R, Chen W, Wahl SM, Swaim W, Engelholm LH, Behrendt N, Bugge TH (2002) Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene 21:3765–3779

  29. Meyer-Hoffert U, Wu Z, Schroder JM (2009) Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor. PLoS One 4:e4372

  30. Meyer-Hoffert U, Wu Z, Kantyka T, Fischer J, Latendorf T, Hansmann B, Bartels J, He Y, Gläser R, Schröder JM (2010) Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. J Biol Chem 285:32174–32181

  31. Miyai M, Matsumoto Y, Yamanishi H, Yamamoto-Tanaka M, Tsuboi R, Hibino T (2014) Keratinocyte-specific mesotrypsin contributes to the desquamation process via kallikrein activation and LEKTI degradation. J Invest Dermatol 134:1665–1674

  32. Nakane H, Ishida-Yamamoto A, Takahashi H, Iizuka H (2002) Elafin, a secretory protein, is cross-linked into the cornified cell envelopes from the inside of psoriatic keratinocytes. J Invest Dermatol 119:50–55

  33. Naoe Y, Hata T, Tanigawa K, Kimura H, Masunaga T (2010) Bidimensional analysis of desmoglein 1 distribution on the outermost corneocytes provides the structural and functional information of the stratum corneum. J Dermatol Sci 57:192–198

  34. Ohler A, Debela M, Wagner S, Magdolen V, Becker-Pauly C (2010) Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation. Biol Chem 391:455–460

  35. Raknerud N (1975) The ultrastructure of the interfollicular epidermis of the hairless (hr/hr) mouse. III. Desmosomal transformation during keratinization. J Ultrastruct Res 52:32–51

  36. Rawlings AV, Voegeli R (2013) Stratum corneum proteases and dry skin conditions. Cell Tissue Res 351:217–235

  37. Sales KU, Masedunskas A, Bey AL, Rasmussen AL, Weigert R, List K, Szabo R, Overbeek PA, Bugge TH (2010) Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat Genet 42:676–683

  38. Scott FL, Sun J, Whisstock JC, Kato K, Bird PI (2007) SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes. J Biochem 142:435–442

  39. Sotiropoulou G, Pampalakis G, Diamandis EP (2009) Functional roles of human kallikrein-related peptidases. J Biol Chem 284:32989–32994

  40. Ya-Xian Z, Suetake T, Tagami H (1999) Number of cell layers of the stratum corneum in normal skin—relationship to the anatomical location on the body, age, sex and physical parameters. Arch Dermatol Res 291:555–559

  41. Zeeuwen PL, Ishida-Yamamoto A, van Vlijmen-Willems IM, Cheng T, Bergers M, Iizuka H, Schalkwijk J (2007) Colocalization of cystatin M/E and cathepsin V in lamellar granules and corneodesmosomes suggests a functional role in epidermal differentiation. J Invest Dermatol 127:120–128

  42. Zeeuwen PL, Cheng T, Schalkwijk J (2009) The biology of cystatin M/E and its cognate target proteases. J Invest Dermatol 129:1327–1338

Download references

Conflicts of interest

The authors have no conflicting interests to declare.

Author information

Correspondence to Akemi Ishida-Yamamoto.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ishida-Yamamoto, A., Igawa, S. The biology and regulation of corneodesmosomes. Cell Tissue Res 360, 477–482 (2015). https://doi.org/10.1007/s00441-014-2037-z

Download citation


  • Corneodesmosin
  • Corneodesmosome
  • Desquamation
  • Kallikrein-related peptidases
  • Lympho-epithelial Kazal-type inhibitor (LEKTI)