Artículo

Martín, M.; Modenutti, C.P.; Peyret, V.; Geysels, R.C.; Darrouzet, E.; Pourcher, T.; Masini-Repiso, A.M.; Martí, M.A.; Carrasco, N.; Nicola, J.P."A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter" (2019) Endocrinology. 160(1):156-168
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Abstract:

The Na+/iodide (I-) symporter (NIS), a glycoprotein expressed at the basolateral plasma membrane of thyroid follicular cells, mediates I- accumulation for thyroid hormonogenesis and radioiodide therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit lower I- transport than normal thyroid tissue (or even undetectable I- transport). Paradoxically, the majority of differentiated thyroid cancers show intracellular NIS expression, suggesting abnormal targeting to the plasma membrane. Therefore, a thorough understanding of the mechanisms that regulate NIS plasma membrane transport would have multiple implications for radioiodide therapy. In this study, we show that the intracellularly facing carboxy-terminus of NIS is required for the transport of the protein to the plasma membrane. Moreover, the carboxy-terminus contains dominant basolateral information. Using internal deletions and site-directed mutagenesis at the carboxy-terminus, we identified a highly conserved monoleucine-based sorting motif that determines NIS basolateral expression. Furthermore, in clathrin adaptor protein (AP)-1B-deficient cells, NIS sorting to the basolateral plasma membrane is compromised, causing the protein to also be expressed at the apical plasma membrane. Computer simulations suggest that the AP-1B subunit σ1 recognizes the monoleucine-based sorting motif in NIS carboxy-terminus. Although the mechanisms by which NIS is intracellularly retained in thyroid cancer remain elusive, our findings may open up avenues for identifying molecular targets that can be used to treat radioiodide-refractory thyroid tumors that express NIS intracellularly.

Registro:

Documento: Artículo
Título:A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter
Autor:Martín, M.; Modenutti, C.P.; Peyret, V.; Geysels, R.C.; Darrouzet, E.; Pourcher, T.; Masini-Repiso, A.M.; Martí, M.A.; Carrasco, N.; Nicola, J.P.
Filiación:Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de CórdobaCórdoba, Argentina
Centro de Investigaciones en Bioquímica Clínica e Inmunología-Consejo Nacional de Investigaciones Científicas y Técnicas (CIBICI-CONICET)Córdoba, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos AiresBuenos Aires, Argentina
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales-Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET)Buenos Aires, Argentina
Laboratoire Transporteurs en Imagerie et Radiothérapie en Oncologie, Université de Nice Sophia Antipolis-Université Côte d'Azur, Faculté de Médecine, Nice, France
Laboratoire Transporteurs en Imagerie et Radiothérapie en Oncologie, Commissariat à l'Energie Atomique, Faculté de Médecine, Nice, France
Department of Cellular and Molecular Physiology, Yale School of Medicine, New HavenCT, United States
Año:2019
Volumen:160
Número:1
Página de inicio:156
Página de fin:168
DOI: http://dx.doi.org/10.1210/en.2018-00603
Handle:http://hdl.handle.net/20.500.12110/paper_19457170_v160_n1_p156_Martin
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:19457170
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19457170_v160_n1_p156_Martin

Citas:

---------- APA ----------
Martín, M., Modenutti, C.P., Peyret, V., Geysels, R.C., Darrouzet, E., Pourcher, T., Masini-Repiso, A.M.,..., Nicola, J.P. (2019) . A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter. Endocrinology, 160(1), 156-168.
http://dx.doi.org/10.1210/en.2018-00603
---------- CHICAGO ----------
Martín, M., Modenutti, C.P., Peyret, V., Geysels, R.C., Darrouzet, E., Pourcher, T., et al. "A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter" . Endocrinology 160, no. 1 (2019) : 156-168.
http://dx.doi.org/10.1210/en.2018-00603
---------- MLA ----------
Martín, M., Modenutti, C.P., Peyret, V., Geysels, R.C., Darrouzet, E., Pourcher, T., et al. "A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter" . Endocrinology, vol. 160, no. 1, 2019, pp. 156-168.
http://dx.doi.org/10.1210/en.2018-00603
---------- VANCOUVER ----------
Martín, M., Modenutti, C.P., Peyret, V., Geysels, R.C., Darrouzet, E., Pourcher, T., et al. A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter. Endocrinology. 2019;160(1):156-168.
http://dx.doi.org/10.1210/en.2018-00603