TY - JOUR
T1 - Cleavage of Nidogen-1 by Cathepsin S Impairs Its Binding to Basement Membrane Partners
AU - Sage, Juliette
AU - Leblanc-Noblesse, Emmanuelle
AU - Nizard, Carine
AU - Sasaki, Takako
AU - Schnebert, Sylvianne
AU - Perrier, Eric
AU - Kurfurst, Robin
AU - Brömme, Dieter
AU - Lalmanach, Gilles
AU - Lecaille, Fabien
PY - 2012/8/28
Y1 - 2012/8/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865524320&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0043494
DO - 10.1371/journal.pone.0043494
M3 - Article
C2 - 22952693
AN - SCOPUS:84865524320
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e43494
ER -