Abstract: Series 116, Lecture 7

The Harvey Lectures Series 116 (2022—2023)

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Lecture #7: Thursday, May 18, 2023 — Watch Video of Lecture

New frontiers in the study of the Na+/I- symporter (NIS): Insights into its structure, mechanism, and pathophysiology

Nancy Carrasco, MD, PhD

Nancy Carrasco, MD, PhD

Professor and Chair, Molecular Physiology and Biophysics

Vanderbilt University

Nashville, Tennessee

Dr Carrasco's Website

The Na+/I- symporter (NIS) is the plasma membrane glycoprotein that mediates active I- transport in the thyroid and other tissues. In the thyroid, NIS-mediated I- uptake plays a key physiological role: it is the first step in the biosynthesis of the thyroid hormones, of which iodine is an essential constituent. These hormones are crucial for the development of the central nervous system, the musculoskeletal system, and the lungs in the fetus and newborn, and also for intermediary metabolism at all ages. NIS is of critical significance in thyroid physiology and has, since the 1940s, been at the center of the radioiodide-based treatment for thyroid cancer, the most effective targeted radiation cancer therapy devised to date. However, nothing was known about NIS at the molecular level until we cloned the cDNA coding for it, which allowed us to begin to characterize this remarkable protein in great detail. I will discuss the current state of our understanding of the structure/function properties of NIS, including what we have learned by characterizing I- transport deficiency (ITD)- causing NIS mutations found in patients, as well as the fact that NIS translocates a variety of substrates, including the environmental pollutant perchlorate. I will also present insights into the workings of NIS yielded by the long-awaited structure of the protein, which we recently obtained. NIS has thus far been an unending source of surprises, and there is every indication that it will continue to be.