Creation of a New Method to Refold the Membrane Protein Mutants for Curing of Hereditary Hearing Loss

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The SLC26A4 gene encodes the transmembrane protein pendrin, which is involved in the conditioning of the ion concentration in the endolymph of the inner ear. Mutations in the SLC26A4 gene cause sensorineuronal hearing loss. However, the mechanisms responsible for such loss have remained unknown. In this study, therefore, cellular localization and anion exchanger activity were analyzed by using HEK293 cells transfected with mutant genes. First, 10 pendrin mutants reported in Japanese patients were constructed. Immunofluorescent staining of the cellular localization of the pendrin mutants revealed that normal pendrin was transported to the plasma membrane ; however, 8 mutants were retained in the cytoplasm. Furthermore, we analyzed whether salicylate, as a pharmacological chaperone, restored the function. Incubation with 10 mM of salicylate of the cells transfected with the mutants induced the transport of 4 pendrin mutants from the cytoplasm to the plasma membrane and recovered the anion exchanger activity.