“Thyroid functions of mouse cathepsins b, K and l
Open accessAbstract
Thyroid function depends on processing of the prohormone thyroglobulin by sequential proteolytic events. From in vitro analysis it is known that cysteine proteinases mediate proteolytic processing of thyroglobulin. Here, we have analyzed mice with deficiencies in cathepsins B, K, L, B and K, or K and L in order to investigate which of the cysteine proteinases is most important for proteolytic processing of thyroglobulin in vivo. Immunolabeling demonstrated a rearrangement of the endocytic system and a redistribution of extracellularly located enzymes in thyroids of cathepsin-deficient mice. Cathepsin L was upregulated in thyroids of cathepsin K(-/-) or B(-/-)/K(-/-) mice, suggesting a compensation of cathepsin L for cathepsin K deficiency. Impaired proteolysis resulted in the persistence of thyroglobulin in the thyroids of mice with deficiencies in cathepsin B or L. The typical multilayered appearance of extracellularly stored thyroglobulin was retained in cathepsin K(-/-) mice only. These results suggest that cathepsins B and L are involved in the solubilization of thyroglobulin from its covalently cross-linked storage form. Cathepsin K(-/-)/L(-/-) mice had significantly reduced levels of free thyroxine, indicating that utilization of luminal thyroglobulin for thyroxine liberation is mediated by a combinatory action of cathepsins K and L.
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Cathepsins B and L in the lumen are involved in proteolytic solubilization of TG from covalently cross-linked TG globules.
“Cathepsins B and L in the lumen are involved in proteolytic solubilization of TG from covalently cross-linked TG globules (89).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [89]
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Neuronal loss and brain atrophy in mice lacking cathepsins B and L
Felbor, U., Kessler, B., Mothes, W., Goebel, H. H., Ploegh, H. L., Bronson, R. T., & Olsen, B. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112632299 · Cited by 334 · see citing works
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- Deussing, J., et al. 1998. Cathepsins B and D are dispensable for major his- tocompatibility complex class II-mediated antigen presentation. Proc. Natl. Acad. Sci. U. S. A. 95:4516-4521.
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Selenium in human health and disease
Fairweather-Tait, S. J., Bao, Y., Broadley, M. R., Collings, R., Ford, D., Hesketh, J. E., & Hurst, R. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3275 · Cited by 1,330 · see citing works
Multiple cathepsins promote pro-IL-1β synthesis and NLRP3-mediated IL-1β activation
Orlowski, G. M., Colbert, J. D., Sharma, S., Bogyo, M., Robertson, S. A., & Rock, K. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500509 · Cited by 268 · see citing works
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Friedrichs, B., Tepel, C., Reinheckel, T., Deussing, J., von Figura, K., Herzog, V., Peters, C., Saftig, P., & Brix, K.
- Affiliations
- University of Bonn (DE)
- University of Freiburg (DE)
- Corresponding author
- Brix, Klaudia
- Venue
- Journal of Clinical Investigation
- Published
- 2003-06-01
- Volume
- 111
- Issue
- 11
- Pages
- 1733-1745
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC156100
- OpenAlex
- W2083578935
- Cited by
- 226
- References
- 1
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 13 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 12 · 2017: 9 · 2016: 5 · 2015: 10 · 2014: 10 · 2013: 12 · 2012: 12
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- GRO (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- McGill University
- Shriners Hospitals for Children
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- cathepsin B, cathepsin K, cathepsin L, thyroid function, cysteine protease, proteolytic processing, thyroxine release, free thyroxine
- MeSH terms
- Animals, Cathepsin B, Cathepsins, Cysteine Endopeptidases, Endocytosis, Genotype, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Mutation, Thyroglobulin, Thyroid Gland, Thyroxine, Time Factors, Up-Regulation, Microscopy, Confocal, Mice, Cathepsin K, Cathepsin L
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