title: Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties.
abstract: Corneodesmosomes, the modified desmosomes of the uppermost layers of the epidermis, play an important role in corneocyte cohesion. Corneodesmosin is a secreted glycoprotein located in the corneodesmosomal core and covalently linked to the cornified envelope of corneocytes. Its glycine- and serine-rich NH(2)-terminal domain may fold to give structural motifs similar to the glycine loops described in epidermal cytokeratins and loricrin and proposed to display adhesive properties. A chimeric protein comprising human corneodesmosin linked to the transmembrane and cytoplasmic domains of mouse E-cadherin was expressed in mouse fibroblasts to test the ability of corneodesmosin to promote cell-cell adhesion. Classic aggregation assays indicated that corneodesmosin mediates homophilic cell aggregation. Moreover, Ca(2+) depletion showed a moderate effect on aggregation. To assess the involvement of the glycine loop domain in adhesion, full-length corneodesmosin, corneodesmosin lacking this domain, or this domain alone were expressed as glutathione S-transferase fusion proteins and tested for protein-protein interactions by overlay binding assays. The results confirmed that corneodesmosin presents homophilic interactions and indicated that its NH(2)-terminal glycine loop domain is sufficient but not strictly necessary to promote binding. Altogether, these results provide the first experimental evidence for the adhesive properties of corneodesmosin and for the involvement of its glycine loop domain in adhesion.
authors.affiliation: Department of Biology, INSERM Contrat Jeune Formation 96-02, Toulouse-Purpan School of Medicine, University of Toulouse III, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jonca
authors.forename: Marina
authors.initials: M
authors.lastname: Guerrin
authors.forename: Krassimira
authors.initials: K
authors.lastname: Hadjiolova
authors.forename: Cecile
authors.initials: C
authors.lastname: Caubet
authors.forename: Helene
authors.initials: H
authors.lastname: Gallinaro
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology
chemical_list: C109656:CDSN protein, human; D018076:DNA, Complementary; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012694:Serine; D005982:Glutathione Transferase; D014357:Trypsin; D002118:Calcium; D005998:Glycine