Abstract

The long-range objective of this project is the detailed molecular characterization of the Na+/I-symporter (NIS), a key transport protein that catalyzes the active translocation of iodide into the thyroid gland. In the previous funding periods, considerable progress has been made on this project. A cDNA encoding the NIS has been cloned, and functionally expressed in oocytes and COS cells. A structural model for the NIS has been proposed, and the first anti-NIS antibodies have been generated. In addition, electrophysiological analysis of NIS has been carried out in oocytes, and the importance of the aspartic acid #16 residue in NIS function has been investigated.
The specific aims of the present application are: 1) to continue the identification of functionally important amino acid residues and domains of NIS and investigate its topology in the plasma membrane, 2) to elucidate the biogenesis and regulatory mechanisms of NIS, and 3) to explore possible homologies between iodine transporters from different tissues, including the extra-thyroidal iodine accumulation systems present in the salivary gland and gastric mucosa.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041544-10
Application #
6177262
Study Section
Endocrinology Study Section (END)
Program Officer
Haft, Carol R
Project Start
1989-05-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
10
Fiscal Year
2000
Total Cost
$244,216
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Ravera, Silvia; Carrasco, Nancy; Gelernter, Joel et al. (2018) Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders. J Clin Med 7:
Ferrandino, Giuseppe; Kaspari, Rachel R; Spadaro, Olga et al. (2017) Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proc Natl Acad Sci U S A 114:E9172-E9180
Ravera, Silvia; Reyna-Neyra, Andrea; Ferrandino, Giuseppe et al. (2017) The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annu Rev Physiol 79:261-289
Ferrandino, Giuseppe; Kaspari, Rachel R; Reyna-Neyra, Andrea et al. (2017) An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice. Sci Rep 7:5329
Abbott, Geoffrey W (2017) Chansporter complexes in cell signaling. FEBS Lett 591:2556-2576
Abbott, Geoffrey W (2016) Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and KCNE4. FASEB J 30:2959-69
Ferrandino, Giuseppe; Nicola, Juan Pablo; Sánchez, Yuly E et al. (2016) Na+ coordination at the Na2 site of the Na+/I- symporter. Proc Natl Acad Sci U S A 113:E5379-88
Abbott, Geoffrey W (2016) KCNE4 and KCNE5: K(+) channel regulation and cardiac arrhythmogenesis. Gene 593:249-60
Renier, Corinne; Do, John; Reyna-Neyra, Andrea et al. (2016) Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy. Oncotarget 7:54811-54824
Abbott, Geoffrey W (2016) Channel-transporter complexes: an emerging theme in cell signaling. Biochem J 473:3759-3763

Showing the most recent 10 out of 52 publications