Abstract
Desquamation in the mammalian skin is a well-balanced process of producing corneocytes and shedding them from the surface of the skin. The corneodesmosome, which is a modified desmosome, is the main adhesive structure in the cornified cell layer. The major extracellular constituents of corneodesmosomes are desmoglein 1, desmocollin 1, and corneodesmosin. Proteases involved in the degradation of corneodesmosomes and their inhibitors are secreted from lamellar granules in the granular cell layer. Genetic defects in corneodesmosin and protease inhibitors result in accelerated desquamation and severe barrier impairment. Abnormalities in transportation and secretion of lamellar granules underlie ichthyosis seen in certain human diseases.
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References
Madison KC (2003) Barrier function of the skin: “la raison d’etre” of the epidermis. J Invest Dermatol 121:231–241
Elias PM (2005) Stratum corneum defensive functions: an integrated view. J Invest Dermatol 125:183–200
Elias PM (1983) Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 80(suppl):44s–49s
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
Chapman SJ, Walsh A, Jackson SM, Freidmann PS (1991) Lipids, proteins and corneocyte adhesion. Arch Dermatol Res 283:167–173
Egelrud T (2000) Desquamation in the stratum corneum. Acta Derm Venereol Suppl (Stockh) 208:44–45
Chapman SJ, Walsh A (1990) Desmosomes, corneosomes and desquamation. An ultrastructural study of adult pig epidermis. Arch Dermatol Res 282:304–310
Green KJ, Simpson CL (2007) Desmosomes: new perspectives on a classic. J Invest Dermatol 127:2499–2515
Garrod D, Chidgey M (2008) Desmosome structure, composition and function. Biochim Biophys Acta 1778:572–587
Suzuki Y, Koyama J, Moro O, Horii I, Kikuchi K, Tanida M, Tagami H (1996) The role of two endogeneous proteases of the stratum corneum in degradation of desmoglein-1 and their reduced activity in the skin of ichthyotic patients. Br J Dermatol 134:460–464
Simon M, Montézin M, Guerrin M, Durieux J-J, Serre G (1997) Characterization and purification of human corneodesmosin, an epidermal basic glycoprotein associated with corneocyte-specific modified desmosomes. J Biol Chem 272:31770–31776
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
Descargues P, Deraison C, Prost C, Fraitag S, Mazereeuw-Hautier J, D’Alessio M, Ishida-Yamamoto A, Bodemer C, Zambruno G, Hovnanian A (2006) Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. J Invest Dermatol 126:1622–1632
Serre G, Mils V, Haftek M, Vincent C, Croute F, Reano A, Ouhayoun J-P, Bettinger S, Soleihavoup J-P (1991) Identification of late differentiation antigens of human cornified epithelia, expressed in re-organized desmosomes and bound to cross-linked envelope. J Invest Dermatol 97:1061–1072
Jonca N, Guerrin M, Hadjiolova K, Caubet C, Gallinaro H, Simon M, Serre G (2002) Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties. J Biol Chem 277:5024–5029
Simon M, Jonca N, Guerrin M, Haftek M, Bernard D, Caubet C, Egelrud T, Schmidt R, Serre G (2001) Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem 276:20292–20299
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 proteaser” as cathepsin L2. J Invest Dermatol 120:592–600
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
Odland GF, Holbrook K (1981) The lamellar granules of epidermis. Curr Probl Dermatol 9:29–49
Madison KC, Sando GN, Howard EJ, True CA, Gilbert D, Swartzendruber DC, Wertz PW (1998) Lamellar granule biogenesis: a role for ceramide glucosyltransferase, lysosomal enzyme transport, and the Golgi. J Invest Dermatol Symp Proc 3:80–86
Elias PM, Cullander C, Mauro T, Rassner U, Komuves L, Brown BE, Menon GK (1998) The secretory granular cell: the outermost granular cell as a specialized secretory cell. J Invest Dermatol Symp Proc 3:87–100
Norlen L (2001) Skin barrier formation: the membrane folding model. J Invest Dermatol 117:823–829
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
Ishida-Yamamoto A, Simon M, Kishibe M, Miyauchi Y, Takahashi H, Yoshida S, O’Brien TJ, Serre G, Iizuka H (2004) Epidermal lamellar granules transport different cargoes as distinct aggregates. J Invest Dermatol 122:1137–1144
Menon GK, Price LF, Bommannan B, Elias PM, Feingold KR (1994) Selective obliteration of the epidermal calcium gradient leads to enhanced lamellar body secretion. J Invest Dermatol 102:789–795
Ishida-Yamamoto A, Kishibe M, Takahashi H, Iizuka H (2007) Rab11 is associated with epidermal lamellar granules. J Invest Dermatol 127:2166–2170
Sando GN, Zhu H, Weis JM, Richman JT, Wertz PW, Madison KC (2003) Caveolin expression and localization in human keratinocytes suggest a role in lamellar granule biogenesis. J Invest Dermatol 120:531–541
Roelandt T, Giddelo C, Heughebaert C, Denecker G, Hupe M, Crumrine D, Kusuma A, Haftek M, Roseeuw D, Declercq W, Feingold KR, Elias PM, Hachem JP (2009) The “Caveolae Brake Hypothesis” and the epidermal barrier. J Invest Dermatol 129:927–936
Ovaere P, Lippens S, Vandenabeele P, Declercq W (2009) The emerging roles of serine protease cascades in the epidermis. Trends Biochem Sci 34:453–463
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
Lundwall A, Brattsand M (2008) Kallikrein-related peptidases. Cell Mol Life Sci 65:2019–2038
Sotiropoulou G, Pampalakis G, Diamandis EP (2009) Functional roles of human kallikrein-related peptidases. J Biol Chem 284:32989–32994
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
Komatsu N, Tsai B, Sidiropoulos M, Saijoh K, Levesque MA, Takehara K, Diamandis EP (2006) Quantification of eight tissue kallikreins in the stratum corneum and sweat. J Invest Dermatol 126:925–929
Stefansson K, Brattsand M, Ny A, Glas B, Egelrud T (2006) Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum. Biol Chem 387:761–768
Michael IP, Pampalakis G, Mikolajczyk SD, Malm J, Sotiropoulou G, Diamandis EP (2006) Human tissue kallikrein 5 is a member of a proteolytic cascade pathway involved in seminal clot liquefaction and potentially in prostate cancer progression. J Biol Chem 281:12743–12750
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 pHdependent interaction. Mol Biol Cell 18:3607–3619
Watkinson A, Harding C, Moore A, Coan P (2001) Water modulation of stratum corneum chymotryptic enzyme activity and desquamation. Arch Dermatol Res 293:470–476
Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM (2003) pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol 121:345–353
Horikoshi, Igarashi, Uchiwa, Brysk (1999) Role of endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation. Br J Dermatol 141:453–459
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
Magert H-J, Standker L, Kreutzmann P, Zucht H-D, Reinecke M, Sommerhoff CP, Fritz H, Gorssmann W (1999) LEKTI, a novel 15-domain type of human serine proteinase inhibitor. J Biol Chem 274:21499–21502
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
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
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 271:21886–21890
Zeeuwen PL, Cheng T, Schalkwijk J (2009) The biology of cystatin M/E and its cognate target proteases. J Invest Dermatol 129: 1327–1338
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
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
Debela M, Hess P, Magdolen V, Schechter NM, Steiner T, Huber R, Bode W, Goettig P (2007) 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
Debela M, Goettig P, Magdolen V, Huber R, Schechter NM, Bode W (2007) Structural basis of the zinc inhibition of human tissue kallikrein 5. J Mol Biol 373:1017–1031
Descargues P, Deraison C, Bonnart C, Kreft M, Kishibe M, Ishida-Yamamoto A, Elias P, Barrandon Y, Zambruno G, Sonnenberg A, Hovnanian A (2005) Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat Genet 37:56–65
Komatsu N, Saijoh K, Jayakumar A, Clayman GL, Tohyama M, Suga Y, Mizuno Y, Tsukamoto K, Taniuchi K, Takehara K, Diamandis EP (2008) Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients. J Invest Dermatol 128:1148–1159
Zeeuwen PLJM, van Vlijmen-Willems IMJJ, Hendriks W, Merkx GFM, Schalkwijk J (2002) A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification. Hum Mol Genet 11:2867–2875
Hansson L, Backman A, Ny A, Edlund M, Ekholm E, Ekstrand Hammarstrom B, Tornell J, Wallbrandt P, Wennbo H, Egelrud T (2002) Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. J Invest Dermatol 118:444–449
Egberts F, Heinrich M, Jensen J-M, Winoto-Morbach S, Pfeiffer S, Wickel M, Schunck M, Steude J, Saftig P, Proksch E, Schutze S (2004) Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation. J Cell Sci 117:2295–2307
Rickman L, Simrak D, Stevens HP, Hunt DM, King IA, Bryant SP, Eady RAJ, Leigh IM, Arnemann J, Magee AI, Kelsel DP, Buxton RS (1999) N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma. Hum Mol Genet 8:971–976
Wan H, Dopping-Hepenstal PJC, Gratian MJ, Stone MG, Zhu G, Purkis PE, South AP, Keane F, Armstrong DKB, Buxton RS, McGrath JA, Eady RAJ (2004) Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network. Br J Dermatol 150:878–891
Chidgey M, Brakebusch C, Gustafsson E, Cruchley A, Hail C, Kirk S, Merritt A, North A, Tselepis C, Hewitt J, Byrne C, Fassler R, Garrod D (2001) Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation. J Cell Biol 155:821–832
Matsumoto M, Zhou Y, Matsuo S, Nakanishi H, Hirose K, Oura H, Arase S, Ishida-Yamamoto A, Bando Y, Izumi K, Kiyonari H, Oshima N, Nakayama R, Matsushima A, Hirota F, Mouri Y, Kuroda N, Sano S, Chaplin DD (2008) Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology. Proc Natl Acad Sci U S A 105:6720–6724
Leclerc EA, Huchenq A, Mattiuzzo NR, Metzger D, Chambon P, Ghyselinck NB, Serre G, Jonca N, Guerrin M (2009) Corneodesmosin gene ablation induces lethal skin-barrier disruption and hairfollicle degeneration related to desmosome dysfunction. J Cell Sci 122:2699–2709
Sprecher E, Ishida-Yamamoto A, Mizrahi-Koren M, Rapaport D, Goldsher D, Indelman M, Topaz O, Chefetz I, Keren H, O’Brien TJ, Bercovich D, Shalev S, Geiger D, Bergman R, Horowitz M, Mandel H (2005) A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma. Am J Hum Genet 77:242–251
Hong W (2005) SNAREs and traffic. Biochim Biophys Acta 1744:493–517
Hershkovitz D, Mandel H, Ishida-Yamamoto A, Chefetz I, Hino B, Luder A, Indelman M, Bergman R, Sprecher E (2008) Defective lamellar granule secretion in arthrogryposis, renal dysfunction, and cholestasis syndrome caused by a mutation in VPS33B. Arch Dermatol 144:334–340
Jang JY, Kim KM, Kim GH, Yu E, Lee JJ, Park YS, Yoo HW (2009) Clinical characteristics and VPS33B mutations in patients with ARC syndrome. J Pediatr Gastroenterol Nutr 48:348–354
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Ishida-Yamamoto, A., Kishibe, M. Involvement of corneodesmosome degradation and lamellar granule transportation in the desquamation process. Med Mol Morphol 44, 1–6 (2011). https://doi.org/10.1007/s00795-010-0513-4
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DOI: https://doi.org/10.1007/s00795-010-0513-4