Corneodesmosin, a Corneodesmosome-Specific Basic Protein, Is Expressed in the Cornified Epithelia of the Pig, Guinea Pig, Rat, and Mouse
ABSTRACT Proteolysis of corneodesmosin, a 52- to 56-kDa basic protein located in the extracellular part of the modified desmosomes (corneodesmosomes) of human cornified epithelia, is thought to be a key event of desquamation. Three monoclonal antibodies specific for human corneodesmosin were used to search for the expression of the protein in other mammals. Cryosections of pig, guinea pig, rat, and mouse cornified tissues and proteins sequentially extracted from the corresponding epithelia were analyzed by immunofluorescence and immunoblotting, respectively. Two of the antibodies (F28-27 and B17-21) showed, on the epidermis of the four species and on the cornified epithelia of the rat tongue and esophagus, the same labeling as on human epidermis. Cytoplasmic in the lower granular layer, then pericellular microgranular, the labeling progressively disappeared in the lower cornified layer. By contrast, it persisted up to the surface in the rat tail epidermis. The two antibodies immunodetected basic proteins extracted with isotonic buffer from the epidermis of the pig (50 kDa), guinea pig (52 kDa), and mouse (75 kDa) and from the cornified epithelia of the rat (75 kDa). Immunoreactive proteins of lower Mr were also extracted partly with urea and partly with a reducing agent. The third antibody (G36-19) presented the same reactivities except on murine tissues, where it was unreactive. Our results show that the location, the biochemical characteristics, and the processing of corneodesmosin are similar in five mammals, including humans, suggesting an important role for this protein. They open the way to studies of its function in desquamation using various animal models.
- SourceAvailable from: Cecile Calleja
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- "Corneodesmosin was detected as described (Montézin et al. 1997). Frozen sections (10 µm thick) of unfixed epidermis were stained with Nile red and examined by fluorescence microscopy (450 nm). "
ABSTRACT: Using genetic and pharmacological approaches, we demonstrate that both RARgamma/RXRalpha heterodimers involved in repression events, as well as PPARbeta(delta)/RXRalpha heterodimers involved in activation events, are cell-autonomously required in suprabasal keratinocytes for the generation of lamellar granules (LG), the organelles instrumental to the formation of the skin permeability barrier. In activating PPARbeta(delta)/RXRalpha heterodimers, RXRalpha is transcriptionally active as its AF-2 activation function is required and can be inhibited by an RXR-selective antagonist. Within repressing RARgamma/RXRalpha heterodimers, induction of the transcriptional activity of RXRalpha is subordinated to the addition of an agonistic ligand for RARgamma. Thus, the ligand that possibly binds and activates RXRalpha heterodimerized with PPARbeta(delta) cannot be a retinoic acid, as it would also bind RARgamma and relieve the RARgamma-mediated repression, thereby yielding abnormal LGs. Our data also demonstrate for the first time that subordination of RXR transcriptional activity to that of its RAR partner plays a crucial role in vivo, because it allows RXRs to act concomitantly, within the same cell, as heterodimerization partners for repression, as well as for activation events in which they are transcriptionally active.Genes & Development 07/2006; 20(11):1525-38. DOI:10.1101/gad.368706 · 10.80 Impact Factor
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- "Bars, 2 µm. 45–60 kDa, and 36–40 kDa, respectively (Montezin et al. 1997). The intermediate-sized 45–60-kDa cluster seen in wild-type skin was nearly absent in Spink5 −/− skin, and instead, nearly all of the insoluble Cdsn was 36–40 kDa, which could be caused by inappropriately premature proteolysis (Fig. 5B). "
ABSTRACT: Netherton syndrome (NS) is a human autosomal recessive skin disease caused by mutations in the SPINK5 gene, which encodes the putative proteinase inhibitor LEKTI. We have generated a transgenic mouse line with an insertional mutation that inactivated the mouse SPINK5 ortholog. Mutant mice exhibit fragile stratum corneum and perinatal death due to dehydration. Our analysis suggests that the phenotype is a consequence of desmosomal fragility associated with premature proteolysis of corneodesmosin, an extracellular desmosomal component. Our mouse mutant provides a model system for molecular studies of desmosomal stability and keratinocyte adhesion, and for designing therapeutic strategies to treat NS.Genes & Development 11/2004; 18(19):2354-8. DOI:10.1101/gad.1232104 · 10.80 Impact Factor
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- "The western blotting method has been described in detail previously (Monte Âzin et al, 1997). In particular, peroxidase-conjugated sheep immunoglobulins to mouse IgG (Biosys, Compie Ágne, France) were revealed with the ECL western blotting kit (Amersham, Aylesbury, U.K.). "
ABSTRACT: To understand the biochemical abnormalities that underlie the reduced desquamation observed in dry skin, we analyzed corneodesmosome degradation in normal and winter xerosis skin. Western blotting of total proteins from corneocytes obtained by varnish-strippings from the legs of 56 volunteers with normal (26) or xerotic (30) skin was performed using antibodies specific for (corneo)desmosome proteins. In the whole population, the amounts of desmoglein 1 and plakoglobin were found to be correlated, but were not related to the amounts of corneodesmosin. This suggests simultaneous proteolysis for the former proteins differing from that of corneodesmosin. Neither entire desmoplakins nor any proteolysis-derived fragments were detected. The amounts of corneodesmosin, desmoglein 1, and plakoglobin detected were found to be significantly higher in xerotic compared with normal skin extracts. Conventional and freeze-fracture electron microscopy showed the absence of nonperipheral corneodesmosomes in the upper stratum corneum of normal skin but the presence of a significant number of these structures in the same layer of winter xerosis skin. These results provide a more precise description of the proteolysis of corneodesmosome components in the upper cornified layer of the epidermis. They support previous studies demonstrating the importance of corneodesmosome degradation in desquamation and reveal that the nonperipheral corneodesmosomes, which are totally degraded during maturation of the stratum corneum in normal skin, persist in winter xerosis, probably leading to abnormal desquamation.Keywords: desmosomes, epidermis, keratinocytes, proteasesJournal of Investigative Dermatology 12/2000; 116(1):23-30. DOI:10.1046/j.1523-1747.2001.00208.x · 7.22 Impact Factor