Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy

Autores
Martín, Mariano; Geysels, Romina Celeste; Peyret, Victoria; Bernal Barquero, Carlos Eduardo; Masini-Repiso, Ana María; Nicola, Juan Pablo
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.
Fil: Martín, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Geysels, Romina Celeste. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Fil: Peyret, Victoria. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bernal Barquero, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Fil: Masini-Repiso, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
CONGENITAL HYPOTHYROIDISM
DIFFERENTIATED THYROID CANCER
I2 DEFICIENCY DISORDERS
I2 TRANSPORT DEFECT
NA+/I2 SYMPORTER
RADIOIODINE THERAPY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/128769

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network_name_str CONICET Digital (CONICET)
spelling Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapyMartín, MarianoGeysels, Romina CelestePeyret, VictoriaBernal Barquero, Carlos EduardoMasini-Repiso, Ana MaríaNicola, Juan PabloCONGENITAL HYPOTHYROIDISMDIFFERENTIATED THYROID CANCERI2 DEFICIENCY DISORDERSI2 TRANSPORT DEFECTNA+/I2 SYMPORTERRADIOIODINE THERAPYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.Fil: Martín, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Geysels, Romina Celeste. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Peyret, Victoria. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernal Barquero, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Masini-Repiso, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaOxford University Press2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128769Martín, Mariano; Geysels, Romina Celeste; Peyret, Victoria; Bernal Barquero, Carlos Eduardo; Masini-Repiso, Ana María; et al.; Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy; Oxford University Press; Journal of the Endocrine Society; 3; 1; 1-2019; 222-2342472-1972CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jes/article/3/1/222/5230905info:eu-repo/semantics/altIdentifier/doi/10.1210/js.2018-00100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:06Zoai:ri.conicet.gov.ar:11336/128769instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:06.902CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
title Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
spellingShingle Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
Martín, Mariano
CONGENITAL HYPOTHYROIDISM
DIFFERENTIATED THYROID CANCER
I2 DEFICIENCY DISORDERS
I2 TRANSPORT DEFECT
NA+/I2 SYMPORTER
RADIOIODINE THERAPY
title_short Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
title_full Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
title_fullStr Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
title_full_unstemmed Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
title_sort Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy
dc.creator.none.fl_str_mv Martín, Mariano
Geysels, Romina Celeste
Peyret, Victoria
Bernal Barquero, Carlos Eduardo
Masini-Repiso, Ana María
Nicola, Juan Pablo
author Martín, Mariano
author_facet Martín, Mariano
Geysels, Romina Celeste
Peyret, Victoria
Bernal Barquero, Carlos Eduardo
Masini-Repiso, Ana María
Nicola, Juan Pablo
author_role author
author2 Geysels, Romina Celeste
Peyret, Victoria
Bernal Barquero, Carlos Eduardo
Masini-Repiso, Ana María
Nicola, Juan Pablo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CONGENITAL HYPOTHYROIDISM
DIFFERENTIATED THYROID CANCER
I2 DEFICIENCY DISORDERS
I2 TRANSPORT DEFECT
NA+/I2 SYMPORTER
RADIOIODINE THERAPY
topic CONGENITAL HYPOTHYROIDISM
DIFFERENTIATED THYROID CANCER
I2 DEFICIENCY DISORDERS
I2 TRANSPORT DEFECT
NA+/I2 SYMPORTER
RADIOIODINE THERAPY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.
Fil: Martín, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Geysels, Romina Celeste. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Fil: Peyret, Victoria. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bernal Barquero, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Fil: Masini-Repiso, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/128769
Martín, Mariano; Geysels, Romina Celeste; Peyret, Victoria; Bernal Barquero, Carlos Eduardo; Masini-Repiso, Ana María; et al.; Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy; Oxford University Press; Journal of the Endocrine Society; 3; 1; 1-2019; 222-234
2472-1972
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128769
identifier_str_mv Martín, Mariano; Geysels, Romina Celeste; Peyret, Victoria; Bernal Barquero, Carlos Eduardo; Masini-Repiso, Ana María; et al.; Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy; Oxford University Press; Journal of the Endocrine Society; 3; 1; 1-2019; 222-234
2472-1972
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jes/article/3/1/222/5230905
info:eu-repo/semantics/altIdentifier/doi/10.1210/js.2018-00100
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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