Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7.
Corneodesmosin (CDSN), desmoglein 1 (DSG1), and desmocollin 1 (DSC1) are adhesive proteins of the extracellular part of the corneodesmosomes, the junctional structures that mediate corneocyte cohesion. The degradation of these proteins at the epidermis surface is necessary for desquamation. Two serine proteases of the kallikrein family synthesized as inactive precursors have been implicated in this process: the stratum corneum chymotryptic enzyme (SCCE/KLK7/hK7) and the stratum corneum tryptic enzyme (SCTE/KLK5/hK5). Here, we analyzed the capacity of these enzymes to cleave DSG1, DSC1, and epidermal or recombinant forms of CDSN, at an acidic pH close to that of the stratum corneum. SCCE directly cleaved CDSN and DSC1 but was unable to degrade DSG1. But incubation with SCTE induced degradation of the three corneodesmosomal components. Using the recombinant form of CDSN, either with its N-glycan chain or enzymatically deglycosylated, we also demonstrated that oligosaccharide residues do not protect CDSN against proteolysis by SCCE. Moreover, our results suggest that SCTE is able to activate the proform of SCCE. These results strongly suggest that the two kalikreins are involved in desquamation. A model is proposed for desquamation that could be regulated by a precisely controlled protease-protease inhibitor balance.
Caubet
Cécile
C
UMR5165 "Epidermis Differentiation and Rheumatoid Autoimmunity", CNRS-P. Sabatier University (Institut Fédératif de Recherche 30 and INSERM-CNRS-Université P. Sabatier-Centre Hospitalier Universitaire), Toulouse, France.
Jonca
Nathalie
N
Brattsand
Maria
M
Guerrin
Marina
M
Bernard
Dominique
D
Schmidt
Rainer
R
Egelrud
Torbjörn
T
Simon
Michel
M
Serre
Guy
G
D000918:Antibody Specificity; D015820:Cadherins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D051187:Desmocollins; D051183:Desmoglein 1; D003896:Desmosomes / Q000201:enzymology*; D004817:Epidermis / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
C109656:CDSN protein, human; D015820:Cadherins; C081560:DSC1 protein, human; D051187:Desmocollins; D051183:Desmoglein 1; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011994:Recombinant Proteins; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases