title: Auditory mechanotransduction in the absence of functional myosin-XVa.
abstract: In hair cells of all vertebrates, a mechanosensory bundle is formed by stereocilia with precisely graded heights. Unconventional myosin-XVa is critical for formation of this bundle because it transports whirlin and perhaps other molecular components responsible for programmed elongation of stereocilia to the stereocilia tips. A tip of a stereocilium is the site of stereocilia growth and one of the proposed sites of mechano-electrical transduction. In adult shaker 2 mice, a mutation that disables the motor function of myosin-XVa results in profound deafness and abnormally short stereocilia that lack stereocilia links, an indispensable component of mechanotransduction machinery. Therefore, it was assumed that myosin-XVa is required for proper formation of the mechanotransduction apparatus. Here we show that in young postnatal shaker 2 mice, abnormally short stereocilia bundles of auditory hair cells have numerous stereocilia links and 'wild type' mechano-electrical transduction. We compared the mechanotransduction current in auditory hair cells of young normal-hearing littermates, myosin-XVa-deficient shaker 2 mice, and whirler mice that have similarly short stereocilia but intact myosin-XVa at the stereocilia tips. This comparison revealed that the absence of functional myosin-XVa does not disrupt adaptation of the mechanotransduction current during sustained bundle deflection. Thus, the hair cell mechanotransduction complex forms and functions independently from myosin-XVa-based hair bundle morphogenesis.
authors.affiliation: Department of Physiology, University of Kentucky, MS508, Chandler Medical Center, 800 Rose Street, Lexington, KY 40536, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Stepanyan
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology; D003638:Deafness / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000473:pathology / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009218:Myosins / Q000235:genetics* / Q000502:physiology*; D009925:Organ of Corti / Q000166:cytology / Q000473:pathology / Q000502:physiology; D018408:Patch-Clamp Techniques
chemical_list: C114013:Myo15 protein, mouse; D009218:Myosins