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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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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Outer Auditory Hair Cells
Cochlea
Mutation
Kinetics
Mutagenesis
Motor Activity
Cell Membrane
Electric potential
Cell membranes
Amplification
Innovation
Damping
Cells
Acoustic waves

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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 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.",
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The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits. / Homma, Kazuaki; Duan, Chongwen; Zheng, Jing; Cheatham, Mary Ann; Dallos, Peter.

In: Journal of Biological Chemistry, Vol. 288, No. 4, 25.01.2013, p. 2452-2463.

Research output: Contribution to journalArticle

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AU - Homma, Kazuaki

AU - Duan, Chongwen

AU - Zheng, Jing

AU - Cheatham, Mary Ann

AU - Dallos, Peter

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