Mechanotransduction by Hair Cells: Models, Molecules, and Mechanisms

Gillespie, Peter G.; Müller, Ulrich

doi:10.1016/j.cell.2009.09.010

Cited by 402 publications

(369 citation statements)

References 91 publications

Supporting

Mentioning

364

Contrasting

Unclassified

Order By: Relevance

“…The best-known application of the cellpoking assay is the version from auditory physiology, in which hair cell stereocilia are displaced to evoke an electrical signal (31). These experiments, along with specific molecular anatomical features of the stereocilia, underlie the famous tip-link tethergated transduction channel model (43,44), which, interestingly, has a more recent version in which the tether has been proposed to "tent" (i.e., exert tension on) the membrane surrounding the transduction channel (45). In the case of TRAAK and TREK channels it is clear that mechanosensitivity persists in the absence of potential tethers (Figs.…”

Section: Discussionmentioning

confidence: 99%

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels

Brohawn

MacKinnon

2014

Proc. Natl. Acad. Sci. U.S.A.

359

327

View full text Add to dashboard Cite

Mechanosensitive ion channels underlie neuronal responses to physical forces in the sensation of touch, hearing, and other mechanical stimuli. The fundamental basis of force transduction in eukaryotic mechanosensitive ion channels is unknown. Are mechanical forces transmitted directly from membrane to channel as in prokaryotic mechanosensors or are they mediated through macromolecular tethers attached to the channel? Here we show in cells that the K + channel TRAAK (K2P4.1) is responsive to mechanical forces similar to the ion channel Piezo1 and that mechanical activation of TRAAK can electrically counter Piezo1 activation. We then show that the biophysical origins of force transduction in TRAAK and TREK1 (K2P2.1) two-pore domain K + (K2P) channels come from the lipid membrane, not from attached tethers. These findings extend the "force-from-lipid" principle established for prokaryotic mechanosensitive channels MscL and MscS to these eukaryotic mechanosensitive K + channels.mechanosensation | potassium channel | gating | tension | reconstitution

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels

Brohawn

MacKinnon

2014

Proc. Natl. Acad. Sci. U.S.A.

359

327

View full text Add to dashboard Cite

show abstract

“…Tip-link tension may also enhance actin polymerization by increasing MET channel opening probability, and hence the influx of Ca 2+ ions at the stereocilia tip may modulate actin polymerization (27). The rapid [in about 2 d, the time period for the renewal of stereociliary actin (29)] and total disappearance/collapse of the small and medium stereocilia rows contrasts with the maintenance of stereocilia of reduced size in mice defective for myosin XV, whirlin, or espin (30,31) and Fig. 3.…”

Section: Disappearance Of Thementioning

confidence: 99%

Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia

Caberlotto

Michel

Foucher

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

178

View full text Add to dashboard Cite

The mechanotransducer channels of auditory hair cells are gated by tip-links, oblique filaments that interconnect the stereocilia of the hair bundle. Tip-links stretch from the tips of stereocilia in the short and middle rows to the sides of neighboring, taller stereocilia. They are made of cadherin-23 and protocadherin-15, products of the Usher syndrome type 1 genes USH1D and USH1F, respectively. In this study we address the role of sans, a putative scaffold protein and product of the USH1G gene. In Ush1g −/− mice, the cohesion of stereocilia is disrupted, and both the amplitude and the sensitivity of the transduction currents are reduced. In Ush1g fl/fl Myo15-cre +/− mice, the loss of sans occurs postnatally and the stereocilia remain cohesive. In these mice, there is a decrease in the amplitude of the total transducer current with no loss in sensitivity, and the tips of the stereocilia in the short and middle rows lose their prolate shape, features that can be attributed to the loss of tip-links. Furthermore, stereocilia from these rows undergo a dramatic reduction in length, suggesting that the mechanotransduction machinery has a positive effect on F-actin polymerization. Sans interacts with the cytoplasmic domains of cadherin-23 and protocadherin-15 in vitro and is absent from the hair bundle in mice defective for either of the two cadherins. Because sans localizes mainly to the tips of short-and middle-row stereocilia in vivo, we conclude that it belongs to a molecular complex at the lower end of the tip-link and plays a critical role in the maintenance of this link.auditory mechanoelectrical transduction | Usher syndrome type 1 | deafness | conditional knockout mice | organ of Corti

show abstract

“…Movement of the tympanic membrane transmits force sequentially to the three bones of the ossicular chain: the malleus, incus, and stapes. The footplate of the stapes impinges upon the oval window of the cochlea and transmits energy to the cochlear partition that will ultimately displace sensory hair cell bundles, the first step in mechanotransduction (Gillespie and Muller 2009). The movement of the middle ear ossicles is modulated by the tensor tympani and stapedius muscles which insert via tendons into bony prominences on the malleus and stapes, respectively.…”

Section: Introductionmentioning

confidence: 99%

Scleraxis is Required for Differentiation of the Stapedius and Tensor Tympani Tendons of the Middle Ear

Wang

Bresee

Jiang

et al. 2011

JARO

View full text Add to dashboard Cite

Scleraxis (Scx) is a basic helix-loop-helix transcription factor expressed in tendon and ligament progenitor cells and the differentiated cells within these connective tissues in the axial and appendicular skeleton. Unexpectedly, we found expression of the Scx transgenic reporter mouse, Scx-GFP, in interdental cells, sensory hair cells, and cochlear supporting cells at embryonic day 18.5 (E18.5). We evaluated Scx-null mice to gain insight into the function of Scx in the inner ear. Paradoxical hearing loss was detected in Scx-nulls, with 50% of the mutants presenting elevated auditory thresholds. However, Scx-null mice have no obvious, gross alterations in cochlear morphology or cellular patterning. Moreover, we show that the elevated auditory thresholds correlate with middle ear infection. Laser interferometric measurement of sound-induced malleal movements in the infected Scx-nulls demonstrates increased impedance of the middle ear that accounts for the hearing loss observed. The vertebrate middle ear transmits vibrations of the tympanic membrane to the cochlea. The tensor tympani and stapedius muscles insert into the malleus and stapes via distinct tendons and mediate the middle ear muscle reflex that in part protects the inner ear from noise-induced damage. Nothing, however, is known about the development and function of these tendons. Scx is expressed in tendon progenitors at E14.5 and differentiated tenocytes of the stapedius and tensor tympani tendons at E16.5-18.5. Scx-nulls have dramatically shorter stapedius and tensor tympani tendons with altered extracellular matrix consistent with abnormal differentiation in which condensed tendon progenitors are inefficiently incorporated into the elongating tendons. Scx-GFP is the first transgenic reporter that identifies middle ear tendon lineages from the time of their formation through complete tendon maturation. Scx-null is the first genetically defined mouse model for abnormal middle ear tendon differentiation. Scx mouse models will facilitate studies of tendon and muscle formation and function in the middle ear.

show abstract

Mechanotransduction by Hair Cells: Models, Molecules, and Mechanisms

Cited by 402 publications

References 91 publications

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels

Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia

Scleraxis is Required for Differentiation of the Stapedius and Tensor Tympani Tendons of the Middle Ear

Contact Info

Product

Resources

About

Mechanotransduction by Hair Cells: Models, Molecules, and Mechanisms

Cited by 402 publications

References 91 publications

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K + channels

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K + channels

Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia

Scleraxis is Required for Differentiation of the Stapedius and Tensor Tympani Tendons of the Middle Ear

Contact Info

Product

Resources

About

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels

Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K ⁺ channels