The PDZ protein SCRIB regulates sodium/iodide symporter (NIS) expression at the basolateral plasma membrane

MARTÍN, MARIANO; SALLERON, LISA; PEYRET, VICTORIA; GEYSELS, ROMINA CELESTE; DARROUZET, ELISABETH; LINDENTHAL, SABINE; BERNAL BARQUERO, CARLOS EDUARDO; MASINI?REPISO, ANA MARÍA; POURCHER, THIERRY; NICOLA, JUAN PABLO

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Año: 2021 vol. 35

0892-6638

he sodium/iodide symporter (NIS) expresses at the basolateral plasma membrane of the thyroid follicular cell and mediates iodide accumulation required for normal thyroid hormonogenesis. Loss-of-function NIS variants cause congenital hypothyroidism due to impaired iodide accumulation in thyroid follicular cells underscoring the significance of NIS for thyroid physiology. Here we report novel findings derived from the thorough characterization of the nonsense NIS mutant p.R636* NIS-leading to a truncated protein missing the last eight amino acids-identified in twins with congenital hypothyroidism. R636* NIS is severely mislocalized into intracellular vesicular compartments due to the lack of a conserved carboxy-terminal type 1 PDZ-binding motif. As a result, R636* NIS is barely targeted to the plasma membrane and therefore iodide transport is reduced. Deletion of the PDZ-binding motif causes NIS accumulation into late endosomes and lysosomes. Using PDZ domain arrays, we revealed that th