A novel role for flotillin-containing lipid rafts in negative-feedback regulation of thyroid-specific gene expression by thyroglobulin
Open accessAbstract
BACKGROUND: Thyroglobulin (Tg) stored in thyroid follicles regulates follicular function in thyroid hormone (TH) synthesis by suppressing thyroid-specific gene expression in a concentration-dependent manner. Thus, Tg is an intrinsic negative-feedback regulator that can restrain the effect of thyrotropin (TSH) in the follicle. However, the underlying mechanisms by which Tg exerts its prominent autoregulatory effect following recognition by thyrocytes remains unclear. METHODS: In order to identify potential proteins that recognize and interact with Tg, mass spectrometry was used to analyze immunoprecipitated Tg-bound proteins derived from Tg-treated rat thyroid FRTL-5 cells. RESULTS: Flotillin 1 and flotillin 2, two homologs that are integral membrane proteins in lipid rafts, were identified as novel Tg-binding proteins with high confidence. Further studies revealed that flotillins physically interact with endocytosed Tg, and together these proteins redistribute from the cell membrane to cytoplasmic vesicles. Treatment with the lipid raft disrupter methyl-β-cyclodextrin abolished both the endocytosis and the negative-feedback effect of Tg on thyroid-specific gene expression. Meanwhile, siRNA-mediated knockdown of flotillin 1 or flotillin 2 also significantly inhibited Tg effects on gene expression. CONCLUSION: Together these results indicate that flotillin-containing lipid rafts are essential for follicular Tg to be recognized by thyrocytes and exert its negative-feedback effects in the thyroid.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Flotillin can physically interact with endocytosed TG and mediate the negative feedback of TG on TTFs.
“It can physically interact with endocytosed TG and mediate the negative feedback of TG on TTFs (90).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [90]
The indexed Abstract reports that flotillins physically interact with endocytosed Tg and that disrupting flotillin-containing lipid rafts inhibits Tg’s negative-feedback effect on thyroid-specific gene expression. It does not specifically report an effect on TTFs (thyroid transcription factors), so that part of the claim is not established by the retrieved passage. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited by
Sorted by citations
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
- Luo, Y., Akama, T., Okayama, A., Yoshihara, A., Sue, M., Oda, K., Hayashi, M., Ishido, Y., Hirano, H., Hiroi, N., Katoh, R., & Suzuki, K.
- Affiliations
- National Institute of Infectious Diseases (JP)
- Advanced Medical Research Center, Yokohama City University (JP)
- Toho University (JP)
- University of Yamanashi (JP)
- Corresponding author
- Suzuki, Koichi
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2016-11
- Volume
- 26
- Issue
- 11
- Pages
- 1630-1639
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2550372033
- Cited by
- 9
- References
- 0
- Citations by year
- 2026: 1 · 2022: 3 · 2021: 2 · 2019: 2 · 2017: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- pure.teikyo.jp
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (26860713, 15K09444)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- thyroglobulin, flotillin-1, flotillin-2, lipid rafts, negative feedback regulation, thyroid-specific gene expression, thyroid-stimulating hormone, thyroid follicles, FRTL-5 cells, protein-protein interaction, endocytosis, methyl-β-cyclodextrin, thyroid hormone synthesis
- MeSH terms
- Thyroid Epithelial Cells, Animals, Cattle, Cell Line, Endocytosis, Gene Expression Regulation, Membrane Proteins, Microscopy, Fluorescence, Thyroglobulin, Down-Regulation, Protein Isoforms, Hormone Replacement Therapy, Membrane Microdomains, Feedback, Physiological, RNA Interference, RNA, Small Interfering, beta-Cyclodextrins, Immunoprecipitation, Rats, Protein Multimerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
