title: The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.
abstract: Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Homma
authors.forename: Chongwen
authors.initials: C
authors.lastname: Duan
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Cheatham
authors.forename: Peter
authors.initials: P
authors.lastname: Dallos
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics*; D004594:Electrophysiology / Q000379:methods; D057809:HEK293 Cells; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007700:Kinetics; D051379:Mice; D020409:Molecular Motor Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000076988:Sulfate Transporters; D014443:Tyrosine / Q000737:chemistry; D014633:Valine / Q000737:chemistry
chemical_list: D027321:Anion Transport Proteins; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D014443:Tyrosine; D014633:Valine