Book chapter
The Controversial Role of Pendrin in Thyroid Cell Function and in the Thyroid Phenotype in Pendred Syndrome
The Role of Pendrin in Health and Disease, pp.107-118
Springer International Publishing
03/03/2017
DOI: 10.1007/978-3-319-43287-8_7
Abstract
Thyroid hormones are essential for normal development, growth and differentiation of numerous tissues, and metabolic regulation. Structurally, they are unique because they contain iodine. Their synthesis in thyroid follicles thus requires a sufficient nutritional iodide intake, transport into the thyroid cells, and efflux into the follicular lumen where the actual biosynthesis occurs. Historically, Pendred syndrome has been defined by the triad of sensorineural deafness/hearing impairment in combination with goiter and an abnormal organification of iodide. After the identification of the molecular basis of Pendred syndrome, which is caused by biallelic mutations in the SLC26A4/PDS gene, functional studies revealed that pendrin is a multifunctional anion exchanger with affinity, among others, for chloride, iodide, and bicarbonate. This observation, together with the demonstration of pendrin protein expression at the apical membrane of thyrocytes, led to the hypothesis that pendrin might be involved in the efflux of iodide into the follicular lumen. Several experimental observations do indeed support a potential role of pendrin in mediating iodide efflux. However, iodide efflux is also possible in the absence of pendrin, and Slc26a4 −/− knockout mice do not have a thyroidal phenotype. These findings indicate that other exchangers or channels have a redundant or perhaps predominant function. A potential candidate is anoctamin 1 (ANO1/TMEM16A), a calcium-activated anion channel. Anoctamin is also expressed at the apical membrane of thyrocytes, and it has affinity for iodide.
Further studies are needed in order to define the relative physiological role of pendrin and anoctamin in mediating iodide efflux, to characterize their affinity for iodide, and to analyze their species-specific expression pattern.
Details
- Title: Subtitle
- The Controversial Role of Pendrin in Thyroid Cell Function and in the Thyroid Phenotype in Pendred Syndrome
- Creators
- Peter Kopp - Northwestern UniversityAigerim Bizhanova - Harold Washington CollegeLiuska Pesce - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Book chapter
- Publication Details
- The Role of Pendrin in Health and Disease, pp.107-118
- Publisher
- Springer International Publishing; Cham
- DOI
- 10.1007/978-3-319-43287-8_7
- Language
- English
- Date published
- 03/03/2017
- Academic Unit
- Stead Family Department of Pediatrics; Endocrinology and Diabetes
- Record Identifier
- 9984354155702771
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