Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells

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 - https://www.scopus.com/pages/publications/84857788537

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 -