title: Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners.
abstract: Cathepsin S (catS), which is expressed in normal human keratinocytes and localized close to the dermal-epidermal junction (DEJ) degrades some of major basement membrane (BM) constituents. Among them, catS readily hydrolyzed in a time and dose dependent manner human nidogen-1 (nid-1) and nidogen-2, which are key proteins in the BM structure. CatS preferentially cleaved nid-1 at both acid and neutral pH. Hydrolysis of nid-1 was hampered in murine ctss(-/-) spleen lysates pretreated with inhibitors of other classes of proteases. Nid-1 was cleaved within its G2 and G3 globular domains that are both involved in interactions with other BM components. Binding assays with soluble and immobilized ligands indicated that catS altered the formation of complexes between nid-1 and other BM components. Assuming that the cleavage of nid-1 impairs its ability to crosslink with BM partners and perturbs the viscoelastic properties of BM matrix, these data indicate that catS may participate in BM proteolysis, in addition to already identified proteases.
authors.affiliation: INSERM, UMR 1100, Pathologies Respiratoires: protéolyse et aérosolthérapie, Centre d'Etude des Pathologies Respiratoires, Tours, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Sage
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leblanc-Noblesse
authors.forename: Carine
authors.initials: C
authors.lastname: Nizard
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Schnebert
authors.forename: Eric
authors.initials: E
authors.lastname: Perrier
authors.forename: Robin
authors.initials: R
authors.lastname: Kurfurst
authors.forename: Dieter
authors.initials: D
authors.lastname: Brömme
authors.forename: Gilles
authors.initials: G
authors.lastname: Lalmanach
authors.forename: Fabien
authors.initials: F
authors.lastname: Lecaille
mesh_terms: D001485:Basement Membrane / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002403:Cathepsins / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D015603:Keratinocytes / Q000166:cytology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008957:Models, Genetic; D010843:Pichia / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D012212:Rheology / Q000379:methods; D012867:Skin / Q000473:pathology; D020349:Surface Plasmon Resonance
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D008024:Ligands; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; C029967:nidogen; D002403:Cathepsins; C028217:cathepsin S