The distinguishing feature of the outer hair cells of the mammalian cochlea is to elongate and shorten at acoustic frequencies, when their intracellular potential is changed. This """"""""electromotility"""""""" turns these cells into active devices that are able to amplify the sound-evoked mechanical responses of the organ of Corti. The cytosol of these cells is largely free of cytoskeletal elements and their cylindrical shape is maintained mainly by intracellular hydrostatic pressure (turgor), which makes the electromotility possible. We have now characterized the osmotic water permeability of outer hair cells and provided evidence that water is entering the cell through specialized water channels. These water channels were found to localize in the lateral plasma membrane where the outer hair cell """"""""motor"""""""" proteins are located. Using electrophysiology measurements we showed that the expression of the water channels and the """"""""motor"""""""" proteins occur simultaneously at the onset of high sensitivity hearing. In addition we found that water influx into the outer hair cell is regulated by intracellular voltage which may represent an important local feedback mechanism setting up the effectiveness of the OHC motor output. We also used a combination of electron microscopy techniques to describe novel properties of another key element in auditory and vestibular transduction, the tip link. The mechanism of transduction by hair cells is quite different from transduction in other well characterized sensory systems. Unlike visual and olfactory transduction, which rely on G-protein coupled enzyme amplification steps, the auditory and vestibular systems rely on a direct mechanical gating of the transduction channel. Although the tip link is almost certainly part of the mechanical chain that opens the transduction channel, it is less clear whether the tip link itself is the gating spring, the elastic element that stretches during hair-cell stimulation. Our structural experiments, better define the structure of the tip link -- a stiff structure made of a helical double filament with specialized membrane linker structures at either end-- and suggest that the gating spring instead lies in series with the helical segment of the tip link.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000002-12
Application #
6431967
Study Section
(LCB)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Takahashi, Satoe; Sun, Willy; Zhou, Yingjie et al. (2018) Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells. Front Cell Neurosci 12:211
Zhao, Jun; Krystofiak, Evan S; Ballesteros, Angela et al. (2018) Multiple claudin-claudin cis interfaces are required for tight junction strand formation and inherent flexibility. Commun Biol 1:50
Becker, Lars; Schnee, Michael E; Niwa, Mamiko et al. (2018) The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse. Elife 7:
Ebrahim, Seham; Ingham, Neil J; Lewis, Morag A et al. (2016) Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia. Cell Rep 15:935-943
Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul et al. (2016) Hemi-fused structure mediates and controls fusion and fission in live cells. Nature 534:548-52
Krey, Jocelyn F; Krystofiak, Evan S; Dumont, Rachel A et al. (2016) Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid. J Cell Biol 215:467-482
Andrade, Leonardo R; Salles, Felipe T; Grati, M'hamed et al. (2016) Tectorins crosslink type II collagen fibrils and connect the tectorial membrane to the spiral limbus. J Struct Biol 194:139-46
Kurima, Kiyoto; Ebrahim, Seham; Pan, Bifeng et al. (2015) TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia. Cell Rep 12:1606-17
Stager, Sheila V; Freeman, Frances J; Braun, Allen (2015) Characteristics of Fluency and Speech in Two Families With High Incidences of Stuttering. J Speech Lang Hear Res 58:1440-51
Yochelis, A; Ebrahim, S; Millis, B et al. (2015) Self-organization of waves and pulse trains by molecular motors in cellular protrusions. Sci Rep 5:13521

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