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This work was supported by grants PID2019-105303RB I00/AEI/10.13039/501100011033 from Ministerio de Ciencia e Innovacion (MICIN) and B2017/BMD-3724, Tironet2-CM from Comunidad de Madrid (Spain) to P.S.; and SAF2015-69964-R, RTI2018-099343-B-100 from the MICIN, Spain, and Fondo Europeo de Desarrollo Regional to A.D.l.V. P.S. and A.D.l.V. laboratories are supported jointly by CIBERONC CB16/12/00326 from the Instituto de Salud Carlos III (ISCIII). P.K., C.F.-M., and L.M.M. held predoc-toral fellowship from Ministerio de Economia y Competitividad, Universidad Autonoma de Madrid (Spain) and CIBERONC, respectively. D.F.-D. holds a contract associated with Grant SAF2015-69964-R.

Analysis of institutional authors

Fernandez-Mendez CAuthor

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Article

Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes

Publicated to:THYROID. 32 (10): 1259-1270 - 2022-10-01 32(10), DOI: 10.1089/thy.2022.0163

Authors: Koumarianou, Petrina; Fernandez-Mendez, Celia; Fajardo-Delgado, Danae; Mielu, Lidia Mirella; Santisteban, Pilar; De la Vieja, Antonio

Affiliations

CIBERON, 468626, Comunidad de Madrid, Madrid, Spain - Author
CIBERONC, 559892, Madrid, Comunidad de Madrid, Spain - Author
Inst Salud Carlos III ISCIII, Ciber Canc CIBERONC, Madrid, Spain - Author
Inst Salud Carlos III ISCIII, Unidad Tumores Endocrinos UFIEC, Madrid, Spain - Author
Instituto de Investigaciones Biomedicas Alberto Sols, 70694, Cabcer Biology, Madrid, Madrid, Spain. - Author
Instituto de Investigaciones Biomédicas Alberto Sols, 70694, Cancer Biology, Madrid, Madrid, Spain - Author
Instituto de Salud Carlos III, 38176, Endocrine Tumors Unit, Majadahonda, Madrid, Spain. - Author
Instituto de Salud Carlos III, 38176, Unidad de Tumores Endocrinos (UFIEC), Madrid, Comunidad de Madrid, Spain - Author
Univ Autonoma Madrid, Inst Invest Biomed Alberto Sols, CSIC, Madrid UAM, Madrid, Spain - Author
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Abstract

The sodium iodide symporter (NIS) is a transmembrane protein located on the basolateral membrane of thyrocytes. Despite its physiological and clinical relevance, little is known about the mechanisms that mediate NIS subcellular sorting. In the present study, we examined NIS basolateral trafficking in vitro using non-thyroid and thyroid epithelial cells.Immunofluorescence and western blotting were performed to analyze NIS subcellular location and function in cells grown in monolayers under unpolarized and/or polarized conditions. Strategic NIS residues were mutated and binding of NIS to clathrin adaptor complexes was determined by immunoprecipitation.We show that NIS reaches the plasma membrane through a thyroid stimulating hormone-dependent mechanism 24 hours after treatment with the hormone. We demonstrate that NIS basolateral trafficking is a clathrin-mediated mechanism, in which the clathrin adaptor complexes AP-1 (A and B) sort NIS from the trans-Golgi network and recycling endosomes. Specifically, we show that the AP-1B µ1 subunit controls NIS basolateral sorting through common recycling endosomes. In its absence, NIS is apically missorted but remains functional. Additionally, direct NIS basolateral transport from the trans-Golgi network to the basolateral membrane is mediated by AP-1A through clathrin-coated vesicles that also carry the transferrin receptor. Loss of the µ1 subunit of AP-1A is functionally compensated by AP-1B. Furthermore, loss of both subunits diminishes NIS trafficking to the plasma membrane. Finally, we demonstrate that AP-1A binds to the L121 and LL562/563 residues on NIS, whereas AP-1B binds to L583.Our findings highlight the novel involvement of the clathrin-coated machinery in basolateral NIS trafficking. Given that AP-1A expression is reduced in tumors, and its expression correlates with that of NIS, these findings will help uncover new targets in thyroid cancer treatment.

Keywords

ap-1bcancerclathringene-expressionmolecular analysisnis expressionnis traffickingprotein sortingrecognitionrepressionsodium iodide symporterthyroid-stimulating hormonetraffickingtransport-defectAdaptor proteins, vesicular transportAp-1aAp-1bClathrinHormonesHumansIodidesNis traffickingProtein sortingReceptors, transferrinSodiumSodium iodide symporterSodium-iodide symporterSymportersThyrotropinTranscription factor ap-1

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal THYROID due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 24/145, thus managing to position itself as a Q1 (Primer Cuartil), in the category Endocrinology & Metabolism.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.23. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.6 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 5.21 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-09, the following number of citations:

  • WoS: 5
  • Scopus: 8
  • Europe PMC: 4
  • OpenCitations: 4

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 4.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 4 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 11.7.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Koumarianou P) .