Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners

Juliette Sage; Emmanuelle Leblanc-Noblesse; Carine Nizard; Takako Sasaki; Sylvianne Schnebert; Eric Perrier; Robin Kurfurst; Dieter Brömme; Gilles Lalmanach; Fabien Lecaille

doi:10.1371/journal.pone.0043494

Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners

PLoS One. 2012;7(8):e43494. doi: 10.1371/journal.pone.0043494. Epub 2012 Aug 28.

Authors

Juliette Sage¹, Emmanuelle Leblanc-Noblesse, Carine Nizard, Takako Sasaki, Sylvianne Schnebert, Eric Perrier, Robin Kurfurst, Dieter Brömme, Gilles Lalmanach, Fabien Lecaille

Affiliation

¹ INSERM, UMR 1100, Pathologies Respiratoires: protéolyse et aérosolthérapie, Centre d'Etude des Pathologies Respiratoires, Tours, France.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basement Membrane / metabolism*
Calcium-Binding Proteins
Cathepsins / chemistry*
Cell Adhesion Molecules / chemistry*
Cell Adhesion Molecules / metabolism
Dermis / metabolism
Epidermis / metabolism
Humans
Hydrolysis
Keratinocytes / cytology
Ligands
Membrane Glycoproteins / chemistry*
Membrane Glycoproteins / metabolism
Models, Genetic
Pichia / metabolism
Protein Binding
Proteolysis
Rheology / methods
Skin / pathology
Surface Plasmon Resonance

Substances

Calcium-Binding Proteins
Cell Adhesion Molecules
Ligands
Membrane Glycoproteins
NID2 protein, human
nidogen
Cathepsins
cathepsin S

Grants and funding

This work was financially supported by LVMH Recherche (Saint Jean de Braye, France) and by institutional funding from the Institut National de la Santé et de la Recherche Médicale (INSERM). DB was supported by a Canada Research Chair award. JS holds a doctoral fellowship from the Association Nationale de la Recherche Technique (ANRT, France; CIFRE PhD funding). The funders had no rule in study design, data collection and analysis, decision to publish, or preparation of the manuscript.