Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes

[Background]: 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...

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Autores: Koumarianou, Petrina, Fernández-Méndez, Celia, Fajardo-Delgado, Dánae, Mielu, Lidia Mirella, Santisteban, Pilar, Vieja, Antonio de la
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/289453
Acceso en línea:http://hdl.handle.net/10261/289453
Access Level:acceso abierto
Palabra clave:AP-1A
AP-1B
Clathrin
NIS trafficking
Protein sorting
Sodium iodide symporter
id ES_bfc7e2ff36ebb349f267f6b732630d3b
oai_identifier_str oai:digital.csic.es:10261/289453
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
title Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
spellingShingle Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
Koumarianou, Petrina
AP-1A
AP-1B
Clathrin
NIS trafficking
Protein sorting
Sodium iodide symporter
title_short Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
title_full Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
title_fullStr Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
title_full_unstemmed Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
title_sort Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexes
dc.creator.none.fl_str_mv Koumarianou, Petrina
Fernández-Méndez, Celia
Fajardo-Delgado, Dánae
Mielu, Lidia Mirella
Santisteban, Pilar
Vieja, Antonio de la
author Koumarianou, Petrina
author_facet Koumarianou, Petrina
Fernández-Méndez, Celia
Fajardo-Delgado, Dánae
Mielu, Lidia Mirella
Santisteban, Pilar
Vieja, Antonio de la
author_role author
author2 Fernández-Méndez, Celia
Fajardo-Delgado, Dánae
Mielu, Lidia Mirella
Santisteban, Pilar
Vieja, Antonio de la
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Comunidad de Madrid
Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv AP-1A
AP-1B
Clathrin
NIS trafficking
Protein sorting
Sodium iodide symporter
topic AP-1A
AP-1B
Clathrin
NIS trafficking
Protein sorting
Sodium iodide symporter
description [Background]: 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. [Methods]: 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. [Results]: We show that NIS reaches the plasma membrane (PM) through a thyrotropin-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 (TGN) and recycling endosomes (REs). Specifically, we show that the AP-1B μ1 subunit controls NIS basolateral sorting through common REs. In its absence, NIS is apically missorted but remains functional. Additionally, direct NIS basolateral transport from the TGN 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 PM. Finally, we demonstrate that AP-1A binds to the L121 and LL562/563 residues on NIS, whereas AP-1B binds to L583. [Conclusions]: 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/289453
url http://hdl.handle.net/10261/289453
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105303RB-I00
B2017/BMD-3724/Tironet2-CM
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099343-B-I00
info:eu-repo/grantAgreement/MINECO//SAF2015-69964-R
http://dx.doi.org/10.1089/thy.2022.0163
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Basolateral sorting of the sodium/Iodide symporter Is mediated by adaptor protein 1 clathrin adaptor complexesKoumarianou, PetrinaFernández-Méndez, CeliaFajardo-Delgado, DánaeMielu, Lidia MirellaSantisteban, PilarVieja, Antonio de laAP-1AAP-1BClathrinNIS traffickingProtein sortingSodium iodide symporter[Background]: 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. [Methods]: 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. [Results]: We show that NIS reaches the plasma membrane (PM) through a thyrotropin-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 (TGN) and recycling endosomes (REs). Specifically, we show that the AP-1B μ1 subunit controls NIS basolateral sorting through common REs. In its absence, NIS is apically missorted but remains functional. Additionally, direct NIS basolateral transport from the TGN 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 PM. Finally, we demonstrate that AP-1A binds to the L121 and LL562/563 residues on NIS, whereas AP-1B binds to L583. [Conclusions]: 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.This work was supported by grants PID2019-105303RBI00/AEI/10.13039/501100011033 from Ministerio de Ciencia e Innovacio´n (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 predoctoral fellowship from Ministerio de Economia y Competitividad, Universidad Auto´noma de Madrid (Spain) and CIBERONC, respectively. D.F.-D. holds a contract associated with Grant SAF2015-69964-R.Mary Ann LiebertMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Comunidad de MadridInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/289453reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105303RB-I00B2017/BMD-3724/Tironet2-CMinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099343-B-I00info:eu-repo/grantAgreement/MINECO//SAF2015-69964-Rhttp://dx.doi.org/10.1089/thy.2022.0163Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2894532026-05-22T06:33:51Z
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