The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits

Kazuaki Homma*, Chongwen Duan, Jing Zheng, Mary Ann Cheatham, Peter Dallos

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)2452-2463
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number4
DOIs
StatePublished - Jan 25 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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