TY - JOUR
T1 - Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells
AU - Magister, Špela
AU - Obermajer, Natasa
AU - Mirković, Bojana
AU - Švajger, Urban
AU - Renko, Miha
AU - Softić, Adaleta
AU - Romih, Rok
AU - Colbert, Jeff D.
AU - Watts, Colin
AU - Kos, Janko
N1 - Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - In dendritic cells (DCs) cysteine cathepsins play a key role in antigen processing, invariant chain (Ii) cleavage and regulation of cell adhesion after maturation stimuli. Cystatin F, a cysteine protease inhibitor, is present in DCs in endosomal/lysosomal vesicles and thus has a potential to modulate cathepsin activity. In immature DCs cystatin F colocalizes with cathepsin S. After induction of DC maturation however, it is translocated into lysosomes and colocalizes with cathepsin L. The inhibitory potential of cystatin F depends on the properties of the monomer. We showed that the full-length monomeric cystatin F was a 12-fold stronger inhibitor of cathepsin S than the N-terminally processed cystatin F, whereas no significant difference in inhibition was observed for cathepsins L, H and X. Therefore, the role of cystatin F in regulating the main cathepsin S function in DCs, i.e. the processing of Ii, may depend on the form of the monomer present in endosomal/lysosomal vesicles. On the other hand, intact and truncated monomeric cystatin F are both potent inhibitors of cathepsin L and it is likely that cystatin F could regulate its activity in maturing, adherent DCs, controlling the processing of procathepsin X, which promotes cell adhesion via activation of Mac-1 (CD11b/CD18) integrin receptor.
AB - In dendritic cells (DCs) cysteine cathepsins play a key role in antigen processing, invariant chain (Ii) cleavage and regulation of cell adhesion after maturation stimuli. Cystatin F, a cysteine protease inhibitor, is present in DCs in endosomal/lysosomal vesicles and thus has a potential to modulate cathepsin activity. In immature DCs cystatin F colocalizes with cathepsin S. After induction of DC maturation however, it is translocated into lysosomes and colocalizes with cathepsin L. The inhibitory potential of cystatin F depends on the properties of the monomer. We showed that the full-length monomeric cystatin F was a 12-fold stronger inhibitor of cathepsin S than the N-terminally processed cystatin F, whereas no significant difference in inhibition was observed for cathepsins L, H and X. Therefore, the role of cystatin F in regulating the main cathepsin S function in DCs, i.e. the processing of Ii, may depend on the form of the monomer present in endosomal/lysosomal vesicles. On the other hand, intact and truncated monomeric cystatin F are both potent inhibitors of cathepsin L and it is likely that cystatin F could regulate its activity in maturing, adherent DCs, controlling the processing of procathepsin X, which promotes cell adhesion via activation of Mac-1 (CD11b/CD18) integrin receptor.
KW - Cystatin F
KW - Cathepsin
KW - Dendritic cell
KW - Antigen presentation
KW - Adhesion
KW - Integrin receptor
UR - http://www.scopus.com/inward/record.url?scp=84857788537&partnerID=8YFLogxK
U2 - 10.1016/j.ejcb.2012.01.001
DO - 10.1016/j.ejcb.2012.01.001
M3 - Article
C2 - 22365146
AN - SCOPUS:84857788537
SN - 0171-9335
VL - 91
SP - 391
EP - 401
JO - European Journal of Cell Biology
JF - European Journal of Cell Biology
IS - 5
ER -