scholarly journals Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

2016 ◽  
Vol 212 (2) ◽  
pp. 231-244 ◽  
Author(s):  
Andrea Lelli ◽  
Vincent Michel ◽  
Jacques Boutet de Monvel ◽  
Matteo Cortese ◽  
Montserrat Bosch-Grau ◽  
...  
Keyword(s):  
Hair Cells ◽  
Late Onset ◽  
Critical Role ◽  
Normal Hearing ◽  
Hair Bundle ◽  
Class Iii ◽  
Auditory Hair Cells ◽  
Mechanoelectrical Transduction ◽  
Hair Bundles ◽  
Myosin Iiia

The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a−/−Myo3b−/− mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b−/− mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a−/−Myo3b−/− cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a−/−Myo3b−/− stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

scholarly journals My oh my(osin): Insights into how auditory hair cells count, measure, and shape

2016 ◽  
Vol 212 (2) ◽  
pp. 135-137
Author(s):  
Lana M. Pollock ◽  
Shih-Wei Chou ◽  
Brian M. McDermott
Keyword(s):  
Hair Cells ◽  
Molecular Motors ◽  
Hair Bundle ◽  
Sensory Cells ◽  
Auditory Hair Cells ◽  
Cell Biol ◽  
Myosin Iiia

The mechanisms underlying mechanosensory hair bundle formation in auditory sensory cells are largely mysterious. In this issue, Lelli et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509017) reveal that a pair of molecular motors, myosin IIIa and myosin IIIb, is involved in the hair bundle’s morphology and hearing.

scholarly journals Direct mechanical stimulation of tip links in hair cells through DNA tethers

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Aakash Basu ◽  
Samuel Lagier ◽  
Maria Vologodskaia ◽  
Brian A Fabella ◽  
AJ Hudspeth
Keyword(s):  
Magnetic Field ◽  
Field Gradient ◽  
Mechanical Stimulation ◽  
Hair Cells ◽  
Magnetic Field Gradient ◽  
Hair Bundle ◽  
Mechanical Forces ◽  
Mechanoelectrical Transduction ◽  
Superparamagnetic Beads ◽  
Stimulation Of

Mechanoelectrical transduction by hair cells commences with hair-bundle deflection, which is postulated to tense filamentous tip links connected to transduction channels. Because direct mechanical stimulation of tip links has not been experimentally possible, this hypothesis has not been tested. We have engineered DNA tethers that link superparamagnetic beads to tip links and exert mechanical forces on the links when exposed to a magnetic-field gradient. By pulling directly on tip links of the bullfrog's sacculus we have evoked transduction currents from hair cells, confirming the hypothesis that tension in the tip links opens transduction channels. This demonstration of direct mechanical access to tip links additionally lays a foundation for experiments probing the mechanics of individual channels.

scholarly journals Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells

Development ◽  
2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

scholarly journals Dynamics of mechanically coupled hair-cell bundles of the inner ear

2020 ◽  
Author(s):  
Y. Roongthumskul ◽  
J. Faber ◽  
D. Bozovic
Keyword(s):  
Inner Ear ◽  
Auditory System ◽  
Hair Cells ◽  
Coupled System ◽  
Acoustic Energy ◽  
Hair Bundle ◽  
Free Standing ◽  
Physiological Level ◽  
Mechanical Coupling ◽  
Hair Bundles

ABSTRACTThe high sensitivity and effective frequency discrimination of sound detection performed by the auditory system rely on the dynamics of a system of hair cells. In the inner ear, these acoustic receptors are primarily attached to an overlying structure which provides mechanical coupling between the hair bundles. While the dynamics of individual hair bundles have been extensively investigated, the influence of mechanical coupling on the motility of the system of bundles remains underdetermined. We developed a technique of mechanically coupling two active hair bundles, enabling us to probe the dynamics of the coupled system experimentally. We demonstrated that the coupling could enhance the coherence of hair bundles’ spontaneous oscillation as well as their phase-locked response to sinusoidal stimuli, at the calcium concentration in the surrounding fluid near the physiological level. The empirical data were consistent with numerical results from a model of two coupled nonisochronous oscillators, each displaying a supercritical Hopf bifurcation. The model revealed that weak coupling can poise the system of unstable oscillators closer to the bifurcation by a shift in the critical point. In addition, the dynamics of strongly coupled oscillators far from criticality suggested that individual hair bundles may be regarded as nonisochronous oscillators. An optimal degree of nonisochronicity was required for the observed tuning behavior in the coherence of autonomous motion of the coupled system.STATEMENT OF SIGNIFICANCEHair cells of the inner ear transduce acoustic energy into electrical signals via a deflection of hair bundles. Unlike a passive mechanical antenna, a free-standing hair bundle behaves as an active oscillator that can sustain autonomous oscillations, as well as amplify a low-level stimulus. Hair bundles under physiological conditions are elastically coupled to each other via an extracellular matrix. Therefore, the dynamics of coupled nonlinear oscillators underlie the performance of the peripheral auditory system. Despite extensive theoretical investigations, there are limited experimental evidence that support the significance of coupling on hair bundle motility. We develop a technique to mechanically couple hair bundles and demonstrate the benefits of coupling on hair bundle spontaneous motility.

Auditory Hair Cells and Sensory Transduction

2017 ◽  
Author(s):  
Jeffrey R. Holt ◽  
Gwenaëlle S.G. Géléoc
Keyword(s):  
Hair Cells ◽  
Water Movement ◽  
Semicircular Canals ◽  
Linear Acceleration ◽  
Sensory Transduction ◽  
Hair Bundle ◽  
Apical Surface ◽  
Mechanical Stimuli ◽  
Auditory Hair Cells ◽  
Aquatic Vertebrates

The organs of the vertebrate inner ear respond to a variety of mechanical stimuli: semicircular canals are sensitive to angular velocity, the saccule and utricle respond to linear acceleration (including gravity), and the cochlea is sensitive to airborne vibration, or sound. The ontogenically related lateral line organs, spaced along the sides of aquatic vertebrates, sense water movement. All these organs have a common receptor cell type, which is called the hair cell, for the bundle of enlarged microvilli protruding from its apical surface. In different organs, specialized accessory structures serve to collect, filter, and then deliver these physical stimuli to the hair bundles. The proximal stimulus for all hair cells is deflection of the mechanosensitive hair bundle. Hair cells convert mechanical information contained within the temporal pattern of hair bundle deflections into electrical signals, which they transmit to the brain for interpretation.

scholarly journals Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles

2020 ◽  
Vol 117 (48) ◽  
pp. 30722-30727
Author(s):  
R. G. Alonso ◽  
M. Tobin ◽  
P. Martin ◽  
A. J. Hudspeth
Keyword(s):  
Hair Bundle ◽  
Fast Recovery ◽  
Mechanoelectrical Transduction ◽  
Hair Bundles ◽  
Protocadherin 15 ◽  
Cadherin 23 ◽  
The Brain ◽  
Intense Stimulation

Hearing and balance rely on the capacity of mechanically sensitive hair bundles to transduce vibrations into electrical signals that are forwarded to the brain. Hair bundles possess tip links that interconnect the mechanosensitive stereocilia and convey force to the transduction channels. A dimer of dimers, each of these links comprises two molecules of protocadherin 15 (PCDH15) joined to two of cadherin 23 (CDH23). The “handshake” that conjoins the four molecules can be disrupted in vivo by intense stimulation and in vitro by exposure to Ca2+chelators. Using hair bundles from the rat’s cochlea and the bullfrog’s sacculus, we observed that extensive recovery of mechanoelectrical transduction, hair bundle stiffness, and spontaneous bundle oscillation can occur within seconds after Ca2+chelation, especially if hair bundles are deflected toward their short edges. Investigating the phenomenon in a two-compartment ionic environment that mimics natural conditions, we combined iontophoretic application of a Ca2+chelator to selectively disrupt the tip links of individual frog hair bundles with displacement clamping to control hair bundle motion and measure forces. Our observations suggest that, after the normal Ca2+concentration has been restored, mechanical stimulation facilitates the reconstitution of functional tip links.

Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction

1992 ◽  
Vol 68 (3) ◽  
pp. 927-932 ◽  
Author(s):  
W. Denk ◽  
R. M. Keolian ◽  
W. W. Webb
Keyword(s):  
Hair Cells ◽  
Mechanical Response ◽  
Low Frequency ◽  
Initial Deflection ◽  
Published Data ◽  
Adaptation Mechanism ◽  
Mechanical Adaptation ◽  
Mechanoelectrical Transduction ◽  
Displacement Sensitivity ◽  
Hair Bundles

1. Deflections of the mechanosensory hair bundles on frog saccular hair cells were measured interferometrically, with submillisecond temporal and submicrometer spatial resolution, and with subnanometer displacement sensitivity. 2. The direction of the initial bundle deflection (toward the taller stereocilia) in response to a sudden application of aminoglycoside antibiotics shows that the mechanosensory channels are blocked in their mechanically open state. 3. The magnitude of the initial deflection is consistent with published data on the gating swing as derived from the gating compliance. 4. A delayed relaxation and frequently a reversal of the initial deflection were observed and are attributed to the previously reported mechanical adaptation mechanism, which is at least partially controlled by the influx of Ca2+ through the transduction channels. 5. Increases of low-frequency spontaneous motion were found at intermediate blocker concentrations. They can be well accounted for by the fluctuating force exerted on the bundle by the random binding and unbinding of blocker molecules. 6. The mechanical response of the hair bundle to aminoglycosides may be related to their acute and specific ototoxicity.

scholarly journals Sensory Transduction and Adaptation in Inner and Outer Hair Cells of the Mouse Auditory System

2007 ◽  
Vol 98 (6) ◽  
pp. 3360-3369 ◽  
Author(s):  
Eric A. Stauffer ◽  
Jeffrey R. Holt
Keyword(s):  
Hair Cells ◽  
Slow Component ◽  
Outer Hair Cells ◽  
Fast Component ◽  
Sensory Transduction ◽  
Hair Bundle ◽  
Sensory Cells ◽  
Auditory Hair Cells ◽  
Inner Hair Cells ◽  
The Difference

Auditory function in the mammalian inner ear is optimized by collaboration of two classes of sensory cells known as inner and outer hair cells. Outer hair cells amplify and tune sound stimuli that are transduced and transmitted by inner hair cells. Although they subserve distinct functions, they share a number of common properties. Here we compare the properties of mechanotransduction and adaptation recorded from inner and outer hair cells of the postnatal mouse cochlea. Rapid outer hair bundle deflections of about 0.5 micron evoked average maximal transduction currents of about 325 pA, whereas inner hair bundle deflections of about 0.9 micron were required to evoke average maximal currents of about 310 pA. The similar amplitude was surprising given the difference in the number of stereocilia, 81 for outer hair cells and 48 for inner hair cells, but may be reconciled by the difference in single-channel conductance. Step deflections of inner and outer hair bundles evoked adaptation that had two components: a fast component that consisted of about 60% of the response occurred over the first few milliseconds and a slow component that consisted of about 40% of the response followed over the subsequent 20–50 ms. The rate of the slow component in both inner and outer hair cells was similar to the rate of slow adaptation in vestibular hair cells. The rate of the fast component was similar to that of auditory hair cells in other organisms and several properties were consistent with a model that proposes calcium-dependent release of tension allows transduction channel closure.

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