The ESF Meeting on „The Proteomics, Epigenetics and Pharmacogenetics of Pendrin“

Abstract

Human pendrin (SCL26A4, PDS) is a 780 amino acid integral membrane protein with transport function. It acts as an electroneutral, sodium-independent anion exchanger for a wide range of anions, such as iodide, chloride, formate, bicarbonate, hydroxide and thiocyanate. Pendrin expression was originally described in the thyroid gland, kidney and inner ear. Accordingly, pendrin mutations with reduction or loss of transport function result in thyroid and inner ear abnormalities, manifested as syndromic (Pendred syndrome) and non-syndromic hearing loss with an enlarged vestibular aqueduct (ns-EVA). Pendred syndrome, the most common form of syndromic deafness, is an autosomal recessive disease characterized by sensorineural deafness due to inner ear malformations and a partial iodide organification defect that may lead to thyroid goiter. Later, it became evident that not only pendrin loss of function, but also up-regulation could participate in the pathogenesis of human diseases. Indeed, despite the absence of kidney dysfunction in Pendred syndrome patients, evidence exists that pendrin also plays a crucial role in this organ, with a potential involvement in the pathogenesis of hypertension. In addition, recent data underscore the role of pendrin in exacerbations of respiratory distresses including bronchial asthma and chronic obstructive pulmonary disease (COPD). Pendrin expression in other organs such as mammary gland, testis, placenta, endometrium and liver point to new, underscored pendrin functions that deserve to be further investigated.

A FRET-Based Approach for Quantitative Evaluation of Forskolin-Induced Pendrin Trafficking at the Plasma Membrane in Bronchial NCI H292 Cells

“…Recent studies have demonstrated that not only loss of function, but also up-regulation of pendrin activity might play a key role in the onset of several human disorders [5], underlying the necessity for reliable tools for quantitative detection of membrane-expressed pendrin under different patho/physiological conditions. FRET technology was first described as a powerful tool for studying protein-protein interactions in living cells [35].…”

“…These biophysical properties are fundamental to the multiple physiological functions of the transporter and its involvement in many pathological processes. In line with this, pendrin is expressed in different tissues and organs such as the thyroid, kidney, inner ear, mammary gland, testis, placenta, endometrium, lung, ameloblasts and liver [4,5,6,7]. Loss of function mutations in pendrin protein cause Pendred syndrome, an autosomal recessive inherited disease characterized by severe bilateral hearing loss, inner ear anomalies and a partial iodide organification defect that may lead to the development of euthyroid goiter or hypothyroidism [8,9,10,11].…”

Sgk1 Sensitive Pendrin Expression in Murine Platelets

“…Pendrin (SLC26A4), an exchanger transporting anions, such as chloride, bicarbonate and iodide [1,2,3], is expressed in a wide variety of tissues, including thyroid gland, inner ear, kidney, lung, liver and heart [4,5,6]. SLC26A4 is required for adequate development of the inner ear [7,8] and it has been suggested that the carrier is involved in thyroid iodide transport [5,9,10].…”

Synopsis of the 48thAnnual Meeting of the Lake Cumberland Biological Transport Group and the Second Biannual Meeting of the Pendrin Consortium

“…The Pendrin Consortium was founded two years ago as a spin-off from an exploratory workshop funded by the European Science Foundation (ESF) in Leogang, Austria [1]. The members planned to meet biannually since then, alternating the location of the meeting between Europe and the USA.…”

“…Pendrin (SLC26A4, PDS) is a transport protein whose malfunction or up regulation may be associated with the onset or exacerbation of a broad spectrum of diseases, including syndromic or non-syndromic deafness, hypertension, asthma and chronic obstructive pulmonary disease (COPD). “Proteomics” within this collaboration refers to how the pendrin protein alone or in conjunction with other proteins impacts the observed function; “epigenetics” refers to how inherited genetic information and genetic information not encoded in the DNA sequence translates to variations in the overall function of pendrin; and finally, “pharmacogenetics” explores how genetic differences in the pendrin gene could be translated into differences in the way that possible drugs affect pendrin function [1]. …”