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Wang Y, Xiang YY, Sugihara J, et al. XB130 plays an essential role in folliculogenesis through mediating interactions between microfilament and microtubule systems in thyrocytes. Thyroid. 2021;doi: 10.1089/thy.2021.0461.
Wang, Y., Xiang, Y. Y., Sugihara, J., Lu, W. Y., Liao, X. H., Arvan, P., Refetoff, S., & Liu, M. (2021). XB130 plays an essential role in folliculogenesis through mediating interactions between microfilament and microtubule systems in thyrocytes. Thyroid : official journal of the American Thyroid Association, . https://doi.org/10.1089/thy.2021.0461
Wang, Yingchun, et al. "XB130 plays an essential role in folliculogenesis through mediating interactions between microfilament and microtubule systems in thyrocytes." Thyroid : official journal of the American Thyroid Association vol. (2021). doi: https://doi.org/10.1089/thy.2021.0461
Wang Y, Xiang YY, Sugihara J, Lu WY, Liao XH, Arvan P, Refetoff S, Liu M. XB130 plays an essential role in folliculogenesis through mediating interactions between microfilament and microtubule systems in thyrocytes. Thyroid. 2021 Oct 15; doi: 10.1089/thy.2021.0461. Epub 2021 Oct 15. PMID: 34652970.
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Thyroid. 2021 Oct 15; doi: 10.1089/thy.2021.0461. Epub 2021 Oct 15.

XB130 plays an essential role in folliculogenesis through mediating interactions between microfilament and microtubule systems in thyrocytes.

Thyroid : official journal of the American Thyroid Association

Yingchun Wang, Yun-Yan Xiang, Junichi Sugihara, Wei-Yang Lu, Xiao-Hui Liao, Peter Arvan, Samuel Refetoff, Mingyao Liu

Affiliations

  1. University Health Network, 7989, PMCRT 2-501, 101 College street, Toronto, Toronto, Ontario, Canada, M5G 0A3; [email protected].
  2. University Health Network, 7989, 101 College Street, Toronto, Ontario, Canada, M5G 1L7; [email protected].
  3. University Health Network, 7989, Latner Thoracic Surgery Research Laboratories, Toronto, Ontario, Canada; [email protected].
  4. University of Western Ontario, 6221, London, Ontario, Canada; [email protected].
  5. University of Chicago, Medicine, Chicago, Illinois, United States; [email protected].
  6. University of Michigan, 1259, Ann Arbor, Michigan, United States; [email protected].
  7. The University of Chicago, Medicine , 5841 South Maryland Avenue, MC 3090, Chicago, Illinois, United States, 60637-1470; [email protected].
  8. University of Toronto, 7938, Surgery, 101 College Street, Toronto, Ontario, Canada, M5S 1L7.
  9. University Health Network, 7989, Toronto, Canada, M5G 2C4; [email protected].

PMID: 34652970 DOI: 10.1089/thy.2021.0461

Abstract

BACKGROUND: XB130 (actin filament associated protein 1 like 2, AFAP1L2) is a thyroid-abundant adaptor/scaffold protein. Xb130-/- mice exhibit transient growth retardation postnatally due to congenital hypothyroidism with diminished thyroglobulin iodination and release at both embryonic and early postnatal stages, due to disorganized thyroid apical membrane structure and function. We hypothesized that XB130 is crucial for polarity and folliculogenesis by mediating proper cytoskeletal structure and function in thyrocytes.

METHODS: Primary thyrocytes isolated from thyroid glands of Xb130-/- mice and their wildtype littermates at post-natal week 2 were cultured in 10% Matrigel for different time periods. Folliculogenesis was studied with immunofluorescent staining followed by confocal microscopy. Cells were also transfected to express human XB130-GFP (or GFP only controls) before morphological analysis. Cytoskeletal structures from embryo and post-natal thyroid glands were also studied.

RESULTS: In 3D cultures of thyrocytes, XB130, aligned with actin filaments, participated in defining the site of apical membrane formation and coalescence to form a thyroid follicle lumen. Xb130-/- thyrocytes displayed delayed folliculogenesis, reduced recruitment of a microtubule associated proteins and disorganized acetylated-tubulin under the apical membrane, resulting in delayed folliculogenesis with reduced efficiency in the formation of thyroid follicle lumen.

CONCLUSION: XB130 critically regulates thyrocyte polarization by functioning as a link between the actin filament cortex and microtubule network at the apical membrane of thyrocytes. Defects of adaptor scaffold proteins may affect cellular polarity, cytoskeletal structure and function and result in disorders of epithelial function, such as congenital hypothyroidism.

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