Interdependence of thyroglobulin processing and thyroid hormone export in the mouse thyroid gland
Open accessAbstract
Thyroid hormone (TH) target cells need to adopt mechanisms to maintain sufficient levels of TH to ensure regular functions. This includes thyroid epithelial cells, which generate TH in addition to being TH-responsive. However, the cellular and molecular pathways underlying thyroid auto-regulation are insufficiently understood. In order to investigate whether thyroglobulin processing and TH export are sensed by thyrocytes, we inactivated thyroglobulin-processing cathepsins and TH-exporting monocarboxylate transporters (Mct) in the mouse. The states of thyroglobulin storage and its protease-mediated processing and degradation were related to the levels of TH transporter molecules by immunoblotting and immunofluorescence microscopy. Thyroid epithelial cells of cathepsin-deficient mice showed increased Mct8 protein levels at the basolateral plasma membrane domains when compared to wild type controls. While the protein amounts of the thyroglobulin-degrading cathepsin D remained largely unaffected by Mct8 or Mct10 single-deficiencies, a significant increase in the amounts of the thyroglobulin-processing cathepsins B and L was detectable in particular in Mct8/Mct10 double deficiency. In addition, it was observed that larger endo-lysosomes containing cathepsins B, D, and L were typical for Mct8- and/or Mct10-deficient mouse thyroid epithelial cells. These data support the notion of a crosstalk between TH transporters and thyroglobulin-processing proteases in thyroid epithelial cells.…
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The complexity of the TG molecule might fulfil further important roles in endocytosis, regulation of the T3/T4 ratio, TG proteolytic processing and in the trafficking to lysosomes.
“Moreover, the complexity of the TG molecule might fulfil further important roles in endocytosis, regulation of the T3/T4 ratio, TG proteolytic processing and in the trafficking to lysosomes25,26.”
From The structure of human thyroglobulin (2020) · cites this paper as [26]
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Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8
Trajkovic, M., Visser, T. J., Mittag, J., Horn, S., Lukas, J., Darras, V. M., Raivich, G., Bauer, K., & Heuer, H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28253 · Cited by 353 · see citing works
Self-citationDumitrescu, A. M., Liao, X.-H., Weiss, R. E., Millen, K., & Refetoff, S. (2006) · Endocrinology · doi:10.1210/en.2006-0390 · Cited by 318 · see citing works
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Groeneweg, S., van Geest, F. S., Peeters, R. P., Heuer, H., & Visser, W. E. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz008 · Cited by 216 · see citing works
Self-citationThe structure of human thyroglobulin
Coscia, F., Taler-Verčič, A., Chang, V. T., Sinn, L., O’Reilly, F. J., Izoré, T., Renko, M., Berger, I., Rappsilber, J., Turk, D., et al. (2020) · Nature · doi:10.1038/s41586-020-1995-4 · Cited by 147 · see citing works
- Authors
- Weber, J., McInnes, J., Kizilirmak, C., Rehders, M., Qatato, M., Wirth, E. K., Schweizer, U., Verrey, F., Heuer, H., & Brix, K.
- Affiliations
- Constructor University (DE)
- Charité – Universitätsmedizin Berlin (DE)
- University of Bonn (DE)
- Leibniz Institute of Environmental Medicine (DE)
- Corresponding author
- Brix, Klaudia
- ORCID
- Venue
- European Journal of Cell Biology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 96
- Issue
- 5
- Pages
- 440-456
- ISSN
- 0171-9335 (ISSN-L)
- OpenAlex
- W2592030686
- Cited by
- 27
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 2 · 2017: 2
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- European Journal of Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Keywords
- thyroid follicular cells, cathepsins, monocarboxylate transporters, MCT8, MCT10, thyroxine, endolysosomes, thyrotoxicosis, mouse thyroid
- MeSH terms
- Animals, Thyroglobulin, Thyroid Gland, Thyroid Hormones, Protein Transport, Membrane Transport Proteins, Monocarboxylic Acid Transporters, Symporters, Mice
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