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

Špela Magister, Natasa Obermajer, Bojana Mirković, Urban Švajger, Miha Renko, Adaleta Softić, Rok Romih, Jeff D. Colbert, Colin Watts, Janko Kos

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    31 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)391-401
    Number of pages11
    JournalEuropean Journal of Cell Biology
    Volume91
    Issue number5
    Early online date23 Feb 2012
    DOIs
    Publication statusPublished - 1 May 2012

    Keywords

    • Cystatin F
    • Cathepsin
    • Dendritic cell
    • Antigen presentation
    • Adhesion
    • Integrin receptor

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  • Cite this

    Magister, Š., Obermajer, N., Mirković, B., Švajger, U., Renko, M., Softić, A., Romih, R., Colbert, J. D., Watts, C., & Kos, J. (2012). Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells. European Journal of Cell Biology, 91(5), 391-401. https://doi.org/10.1016/j.ejcb.2012.01.001