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Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells [Elektronski vir]Senjor, Emanuela ...Cystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell ... stage, called split-anergy. We show that N-glycosylation determines the localization and cellular function of cystatin F. Cystatin F mostly exhibited high-mannose glycosylation in U-937 cells, both high-mannose and complex glycosylation in NK-92 and primary NKs, and predominantly complex glycosylation in super-charged NKs. Manipulating N-glycosylation with kifunensine increased high-mannose glycosylation of cystatin F and lysosome localisation, which decreased cathepsin C activity and reduced NK cytotoxicity. Mannose-6-phosphate could significantly reduce the internalization of extracellular cystatin F. By comparing NK cells with different cytotoxic potentials, we found that high-mannose cystatin F was strongly associated with lysosomes and cathepsin C in NK-92 cell line. In contrast, in highly cytotoxic super-charged NKs, cystatin F with complex glycosylation was associated with the secretory pathway and less prone to inhibit cathepsin C. Modulating glycosylation to alter cystatin F localisation could increase the cytotoxicity of NK cells, thereby enhancing their therapeutic potential for treating cancer patients.Source: Cellular and molecular life sciences. - ISSN 1420-9071 (Vol. 81, iss. 1, art. 8, 2024, 19 str.)Type of material - e-article ; adult, seriousPublish date - 2024Language - englishCOBISS.SI-ID - 177482499
Author
Senjor, Emanuela |
Pirro, Martina |
Švajger, Urban |
Prunk, Mateja, farmacevtka |
Sabotič, Jerica |
Jewett, Anahid |
Hensbergen, Paul J. |
Perišić, Milica |
Kos, Janko, 1959-
Topics
Celična biologija |
Citotoksičnost |
Imunosupresivna biološka zdravila |
cystatin F |
immunosuppression |
NK cells |
N-Glycosylation |
cistatin F |
imunosupresija |
naravne celice ubijalke |
naravne celice ubijalke - glikozilacija
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Senjor, Emanuela | 51713 |
Pirro, Martina | |
Švajger, Urban | 26198 |
Prunk, Mateja, farmacevtka | 37481 |
Sabotič, Jerica | 23576 |
Jewett, Anahid | |
Hensbergen, Paul J. | |
Perišić, Milica | 36596 |
Kos, Janko, 1959- | 04648 |
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