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Inhibitory properties of cystatin F and its localization in U937 promonocyte cells

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Author

Summary, in English

Cystatin F is a recently discovered type II cystatin expressed almost exclusively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with K-i values ranging from 0.17 nm to 0.35 nm, whereas cathepsins S and H were inhibited with 100-fold lower affinities (K-i approximate to 30 nm). The exopeptidases, cathepsins C and X were not inhibited by cystatin F. In order to investigate the biological significance of the inhibition data, the intracellular localization of cystatin F and its potential targets, cathepsins B, H, L, S, C and K, were studied by confocal microscopy in U937 promonocyte cells. Although vesicular staining was observed for all the enzymes, only cathepsins H and X were found to be colocalized with the inhibitor. This suggests that cystatin F in U937 cells may function as a regulatory inhibitor of proteolytic activity of cathepsin H or, more likely, as a protection against cathepsins misdirected to specific cystatin F containing endosomal/lysosomal vesicles. The finding that cystatin F was not colocalized with cystatin C suggests distinct functions for these two cysteine protease inhibitors in U937 cells.

Publishing year

2005

Language

English

Pages

1535-1545

Publication/Series

The FEBS Journal

Volume

272

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Biochemistry and Molecular Biology

Keywords

  • antigen presentation
  • cystatin
  • inhibition
  • cathepsin
  • cysteine protease

Status

Published

ISBN/ISSN/Other

  • ISSN: 1742-464X