Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with pendred syndrome

Silvia Dossena, Valeria Vezzoli, Nadia Cerutti, Claudia Bazzini, Marisa Tosco, Chiara Sironi, Simona Rodighiero, Giuliano Meyer, Umberto Fascio, Johannes Fürst, Markus Ritter, Laura Fugazzola, Luca Persani, Patrick Zorowka, Carlo Storelli, Paolo Beck-Peccoz, Guido Bottà, Markus Paulmichl

Research output: Contribution to journalArticle

Abstract

Background: Malfunction of the SLC26A4 protein leads to prelingual deafness often associated with mild thyroid dysfunction and goiter. It is assumed that SLC26A4 acts as a chloride/anion exchanger responsible for the iodide organification in the thyroid gland, and conditioning of the endolymphatic fluid in the inner ear. Methods: Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4 S28R) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss. Results: Experiments are summarized showing the functional characterization of wild type SLC26A4 and a mutant (S28R), which we described recently. This mutant protein is transposed towards the cell membrane, however, its transport capability is markedly reduced if compared to wild-type SLC26A4. Furthermore, we show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes with iodide, and, in addition, that the chloride uptake can be blocked by NPPB and niflumic acid, whereas DIDS is ineffective. Conclusions: The functional characteristics of SLC26A4 S28R we describe here, are consistent with the clinical phenotype observed in the patient from which the mutant was derived.

Original languageEnglish
Pages (from-to)245-256
Number of pages12
JournalCellular Physiology and Biochemistry
Volume17
Issue number5-6
DOIs
Publication statusPublished - 2006

Keywords

  • Chloride uptake
  • Chloride/bicarbonate exchanger
  • DIDS
  • Ion transport
  • Niflumic acid
  • NPPB
  • Pendred syndrome
  • SLC26A4

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    Dossena, S., Vezzoli, V., Cerutti, N., Bazzini, C., Tosco, M., Sironi, C., Rodighiero, S., Meyer, G., Fascio, U., Fürst, J., Ritter, M., Fugazzola, L., Persani, L., Zorowka, P., Storelli, C., Beck-Peccoz, P., Bottà, G., & Paulmichl, M. (2006). Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with pendred syndrome. Cellular Physiology and Biochemistry, 17(5-6), 245-256. https://doi.org/10.1159/000094137