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

Eur J Cell Biol. 2012 May;91(5):391-401. doi: 10.1016/j.ejcb.2012.01.001. Epub 2012 Feb 23.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cathepsin L / metabolism*
  • Cathepsins / metabolism*
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Cystatins / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Endosomes / metabolism*
  • Female
  • Humans
  • Lysosomes / metabolism*
  • Macrophage-1 Antigen / metabolism
  • Male

Substances

  • Biomarkers, Tumor
  • CST7 protein, human
  • Cystatins
  • Macrophage-1 Antigen
  • Cathepsins
  • CTSL protein, human
  • Cathepsin L
  • cathepsin S