Cohesive Properties of Terminally Differentiated Keratinocytes

Brysk, Miriam M.; Rajaraman, Srinivasan; Penn, Philip; Barlow, Elisia; Bell, Trace

doi:10.1159/000163509

Cited by 6 publications

(2 citation statements)

References 15 publications

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“…Functional experiments will be necessary to test whether this region and the former domain are involved in putative adhesion properties of corneodesmosin. These velcro-related adhesion properties could be, in part, the basis for the observed reaggregation of mechanically dispersed corneocytes and in particular the reformation of corneodesmosomes (31).…”

Section: Discussionmentioning

confidence: 96%

Expression Cloning of Human Corneodesmosin Proves Its Identity with the Product of the S Gene and Allows Improved Characterization of Its Processing during Keratinocyte Differentiation

Guerrin

Simon

Montézin

et al. 1998

Journal of Biological Chemistry

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In human epidermis and other cornified squamous epithelia, corneodesmosin is located in the desmosomes of the upper living layers, and in related structures of the cornified layers, the corneodesmosomes. During maturation of the cornified layers, the protein undergoes a series of cleavages, thought to be a prerequisite of desquamation. Partial amino acid sequencing of corneodesmosin fragments suggested that it is related to the product of the S gene, previously identified in the human major histocompatibility complex.We report the expression cloning of corneodesmosin cDNA from a human epidermis library screened with monoclonal antibodies. Sequencing demonstrated that corneodesmosin is really the product of the S gene. However, analysis of 20 alleles of the gene revealed that its product is 27 amino acids longer than initially reported. Two additional polymorphic sites were described, and the position of the unique intron was ascertained.Corneodesmosin cDNA expression in COS-7 cells led to secretion of the protein. Precise epitope mapping allowed further characterization of the molecular forms of corneodesmosin present in the most superficial cornified layers, where fragments corresponding to the central region of the protein were detected. This indicated a cleavage of the N-and C-terminal domains of corneodesmosin before desquamation. These serineand glycine-rich domains are proposed to mediate an adhesive function.The late stages of the terminal differentiation program in epidermis correspond to cornification, a particular cell death process transforming keratinocytes into anucleated, flattened corneocytes. Stacking of the corneocytes forms the most superficial epidermal layers, designated as the cornified layers or stratum corneum, and is responsible for the mechanical protection of the body. Corneocytes are continually shed from the epidermis surface in the tightly regulated process of desquamation (1, 2).Corneocyte function is achieved by peculiar structures formed during cornification. The cornified cell envelope, a rigid pericellular shell, consists of covalently linked proteins. Its external side is covered by a monomolecular lipid layer, whereas its internal surface is linked to a cytokeratin-rich fibrous matrix that occupies the entire intracellular volume (3, 4). Intercellular structures derived from desmosomes have been described in the stratum corneum. Indeed, considerable morphological modifications of the desmosomes occur when keratinocytes reach the cornified layers. The desmosomal plaque, thought to be incorporated in the cornified cell envelope, is no longer observed, and the characteristic symmetrical trilamellar structure of the extracellular core becomes transformed into a homogeneous electron dense plug (5-9). These structures, called corneodesmosomes, play a major role in stratum corneum cohesion (9 -15). Their degradation, performed at the skin surface, by the stratum corneum chymotryptic enzyme and other less characterized proteases, is required for desquamation (16 -19). Although corneod...

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Section: Discussionmentioning

confidence: 96%

Expression Cloning of Human Corneodesmosin Proves Its Identity with the Product of the S Gene and Allows Improved Characterization of Its Processing during Keratinocyte Differentiation

Guerrin

Simon

Montézin

et al. 1998

Journal of Biological Chemistry

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“…Its high avidity of binding suggests that it plays a role in cell cohesion of the stratum corneum. We have devel oped a comeal aggregation system (analogous to that for erythrocytes) using ether-dispersed comeal cells [2], Reaggregation of the dispersed squames is inhibited by amino sugars, by exogenously added lectins, and by the antibody to the 40-kilodalton glycoprotein [2], We have also been able to recombine structures that resemble the intact tissue [2,3]. Because of the unique lectin-like properties of the 40-kilodalton glycoprotein, we believe that it plays a major role in epidermal desquamation and have named it 'desquamin'.…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of Desquamin to Proteolytic Degradation

Brysk

Bell²,

Rajaraman³

1991

Pathobiology

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The stratum corneum is both a desquamating and degradative tissue; cell contacts become weaker in the outer lamellae and a variety of proteolytic and glycolytic enzymes cleave many macromolecules into free amino acids and saccharides. We have reported on a 40-kilodalton glycoprotein from human stratum corneum; because of its unique lectin-like properties, we believe that it plays a major role in desquamation and have named it desquamin. If desquamin is to function as a lectin during desquamation, it must survive enzymatic degradation in the outer stratum corneum. Accordingly, we treated this glycoprotein with a number of proteinases and found that desquamin is resistant in vitro to most of the types of proteinases that have been reported in the stratum corneum as well as several others that have not been identified as present in the tissue. In the stratum corneum, the lipids of the intercorneal mortar shield the glycoproteins; hence, desquamin is even less likely to be susceptible to endogenous proteolysis in vivo than in vitro.

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Lipids, proteins and corneocyte adhesion

et al. 1991

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Three factors were examined for their relative contribution to corneocyte cohesion in normal adult pig ear: (1) extracellular lipids derived from membrane-coating granules (MCG); (2) corneosomes (modified stratum corneum desmosomes); and (3) corneocyte covalently bound lipid envelopes. Cohesion strength of the outer stratum corneum was measured directly by cohesometry, then altered by removing MCG lipids with solvents of varying potency. Cohesion changes were related to degree of lipid removal and ultrastructural alterations. Trypsin was also used to see if proteolysis of corneosomes promoted squame shedding. Potent solvents increased cohesion in relation to the amount of MCG lipid extracted. Tighter cohesion was due to fusion of the outer leaflets from covalently bound lipid envelopes on adjacent corneocytes. However, lipid envelopes are unlikely to mediate normal stratum corneum cohesion since MCG lipids play a significant anti-cohesive role preventing their apposition. Mild solvents partially removed MCG lipids causing a slight decrease in cohesion compared with untreated samples. This suggests a minor cohesive role for MCG lipids, consistent with maintaining their barrier function. We believe that corneosomes are the major determinant of stratum corneum cohesiveness because, in untreated skin, both cohesion and the number of corneosomes increased from the surface towards the granular layer. Furthermore, corneosome digestion with trypsin induced superficial squame shedding.

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Cohesive Properties of Terminally Differentiated Keratinocytes

Cited by 6 publications

References 15 publications

Expression Cloning of Human Corneodesmosin Proves Its Identity with the Product of the S Gene and Allows Improved Characterization of Its Processing during Keratinocyte Differentiation

Expression Cloning of Human Corneodesmosin Proves Its Identity with the Product of the S Gene and Allows Improved Characterization of Its Processing during Keratinocyte Differentiation

Sensitivity of Desquamin to Proteolytic Degradation

Lipids, proteins and corneocyte adhesion

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