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Does iodide regulate the expression and activity of its apical transporter, pendrin? study in PCCl3 and TSA-201 cells

Grant number: 12/13011-8
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): December 10, 2012
Effective date (End): October 09, 2013
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Maria Tereza Nunes
Grantee:Jamile Calil Silveira
Supervisor abroad: Peter Kopp
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Northwestern University, United States  
Associated to the scholarship:10/05503-2 - Effect of acute administration of iodine in the pendrin gene expression and promoter activity: study in vivo and in vitro, BP.DR

Abstract

The Thyroid Hormones (TH) are essential for the development, growth and metabolism. The TH synthesis needs an efficient apical transport of iodide to follicular lumen. However, the apical efflux of iodide is not well known. The clinical phenotype of patients with Pendred Syndrome and the fact that pendrin can mediate iodide efflux in transfected cells suggest that this anion exchanger may be involved in mediating iodide efflux into the follicular lumen, a key step in thyroid hormone biosynthesis. Functional studies have shown that pendrin is the main apical transporter of iodide. Knowing that 1) apical efflux of iodide is not well known; 2) our group has shown that iodide regulates the mRNA expression of pendrin; 3) it remains unknown whether the intracellular iodide concentration has an impact on pendrin protein localization and thereby on iodide efflux into the follicular lumen; 4) pendrin has phosphorylation sites responsive to TSH, it is aim of this study to determine the insertion of pendrin into the plasma membrane as a function of the intracellular iodide concentration and to determine the insertion and function of human pendrin in response to TSH after mutating the phosphorylation sites, individually or simultaneously, at position S49 (S49A) and T717 (T717A). The effect of iodide on pendrin localization will be studied in rat thyroid PCCL-3 cells, while the effect of the phosphorylation mutants will be studied in transfected TSA-201 cells. The protein content determination will be done by Western Blotting and Biotinylation. Immunofluorescence experiments will be done for analyze the pendrin localization. To analyze the activity of pendrin in different conditions, we will evaluate the intracellular content of 125I, as well as its efflux. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CALIL-SILVEIRA, JAMILE; SERRANO-NASCIMENTO, CAROLINE; KOPP, PETER ANDREAS; NUNES, MARIA TEREZA. Iodide excess regulates its own efflux: a possible involvement of pendrin. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v. 310, n. 7, p. C576-C582, APR 1 2016. Web of Science Citations: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.