A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I– Symporter (NIS)

MARTÍN, MARIANO; MODENUTTI, CARLOS PABLO; PEYRET, VICTORIA; DARROUZET, ELISABETH; GEYSELS, ROMINA CELESTE; POURCHER, THIERRY; MASINI-REPISO, ANA MARÍA; MARTÍ, MARCELO ADRIÁN; CARRASCO, NANCY; NICOLA, JUAN PABLO

ENDOCRINOLOGY

Endocrine Soc

Lugar: Washington; Año: 2018

0013-7227

he Na+/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. Herein, 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 conserv