The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein

Satoe Takahashi, Mary Ann Cheatham, Jing Zheng, Kazuaki Homma*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations


Abstract: A missense mutation, R130S, was recently found in the prestin gene, SLC26A5, of patients with moderate to severe hearing loss (DFNB61). In order to define the pathology of hearing loss associated with this missense mutation, a recombinant prestin construct harboring the R130S mutation (R130S-prestin) was generated, and its functional consequences examined in a heterologous expression system. We found that R130S-prestin targets the plasma membrane but less efficiently compared to wild-type. The voltage operating point and voltage sensitivity of the motor function of R130S-prestin were similar to wild-type prestin. However, the motor activity of R130S-prestin is greatly reduced at higher voltage stimulus frequencies, indicating a reduction in motor kinetics. Our study thus provides experimental evidence that supports a causal relationship between the R130S mutation in the prestin gene and hearing loss found in patients with this missense mutation. Key message: Membrane targeting of prestin is impaired by the R130S missense mutation.The fast motor kinetics of prestin is impaired by the R130S missense mutation.Our study strongly suggests that the prestin R130S missense mutation is pathogenic.

Original languageEnglish (US)
Pages (from-to)1053-1062
Number of pages10
JournalJournal of Molecular Medicine
Issue number9
StatePublished - Sep 1 2016



  • Anion transport
  • DFNB61
  • Electromotility
  • Hearing loss
  • Prestin
  • SLC26A5

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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