Endocrine Abstracts

The Na⁺/I⁻ symporter (NIS), a glycoprotein expressed at the basolateral plasma membrane of thyroid epithelial cells, mediates active I⁻ uptake for the biosynthesis of thyroid hormones and radioiodide transport for diagnosis and treatment in thyroid cancer. Our cloning of the NIS cDNA and generation of anti-NIS antibodies provided the basis to investigate the decrease in I⁻ transport in thyroid cancer relative to healthy thyroid cells. Instead of finding only the expected lower NIS expression, we have reported that in the majority of thyroid cancers, NIS is surprisingly overexpressed as compared to the surrounding tissue but retained intracellularly. Therefore, it is of considerable interest to elucidate the mechanisms underlying NIS plasma membrane targeting, a pursuit that could lead to new therapeutic interventions to increase the sensitivity of radioiodide diagnostic imaging and the effectiveness of radioiodide therapy. We report that the NIS carboxy terminus contains crucial information for NIS trafficking and that the length of the carboxy terminus correlates linearly with functional cell surface expression of the transporter. We also demonstrate that whereas the last four amino acids (E₆₁₅TNL₆₁₈) are not necessary for NIS trafficking, even though they comprise a PDZ binding motif, the 602–614 sequence carries essential determinants for NIS basolateral targeting.