title: The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein.
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.
  
  
  
  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.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60611, USA.
authors.forename: Satoe
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University, Evanston, IL, 60208, USA.|Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Cheatham
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60611, USA.|The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60611, USA. k-homma@northwestern.edu.|The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University, Evanston, IL, 60208, USA. k-homma@northwestern.edu.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Homma
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D027321:Anion Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000838:Anions / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D055724:Electrophysiological Phenomena; D015870:Gene Expression; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D005810:Multigene Family; D009154:Mutation; D011487:Protein Conformation; D021381:Protein Transport; D013329:Structure-Activity Relationship; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters
keywords: Anion transport; DFNB61; Electromotility; Hearing loss; Prestin; SLC26A5