scholarly journals Mechanotransduction-dependent control of stereocilia dimensions and row identity in inner hair cells

2019 ◽  
Author(s):  
Jocelyn F. Krey ◽  
Paroma Chatterjee ◽  
Rachel A. Dumont ◽  
Dongseok Choi ◽  
Jonathan E. Bird ◽  
...  

SummaryActin-rich structures like stereocilia and microvilli are assembled with precise control of length, diameter, and relative spacing. We found that developmental widening of the second-tallest stereocilia rank (row 2) of mouse inner hair cells correlated with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters. EPS8 and the short splice isoform of MYO15A, identity markers for row 1 (tallest), lost their row exclusivity in transduction mutants, a result that was mimicked by block of transduction channels. Likewise, the heterodimeric capping protein subunit CAPZB and its partner TWF2 lost their row 2 tip localization in mutants, and GNAI3 failed to accumulate at row 1 tips. Redistribution of marker proteins was accompanied by increased variability in stereocilia height. Transduction channels thus specify and maintain row identity and control addition of new actin filaments to increase stereocilia diameter.

2017 ◽  
Vol 216 (11) ◽  
pp. 3861-3881 ◽  
Author(s):  
Matthew R. Avenarius ◽  
Jocelyn F. Krey ◽  
Rachel A. Dumont ◽  
Clive P. Morgan ◽  
Connor B. Benson ◽  
...  

Control of the dimensions of actin-rich processes like filopodia, lamellipodia, microvilli, and stereocilia requires the coordinated activity of many proteins. Each of these actin structures relies on heterodimeric capping protein (CAPZ), which blocks actin polymerization at barbed ends. Because dimension control of the inner ear’s stereocilia is particularly precise, we studied the CAPZB subunit in hair cells. CAPZB, present at ∼100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAPZB-interacting protein TWF2. We deleted Capzb specifically in hair cells using Atoh1-Cre, which eliminated auditory and vestibular function. Capzb-null stereocilia initially developed normally but later shortened and disappeared; surprisingly, stereocilia width decreased concomitantly with length. CAPZB2 expressed by in utero electroporation prevented normal elongation of vestibular stereocilia and irregularly widened them. Together, these results suggest that capping protein participates in stereocilia widening by preventing newly elongating actin filaments from depolymerizing.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Hakizimana ◽  
Anders Fridberger

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.


2020 ◽  
Vol 10 (10) ◽  
pp. 3400
Author(s):  
Linas Minkevičius ◽  
Liang Qi ◽  
Agnieszka Siemion ◽  
Domas Jokubauskis ◽  
Aleksander Sešek ◽  
...  

Terahertz (THz) imaging and spectroscopy set-ups require fine optical alignment or precise control of spatial mode profile. We demonstrate universal, convenient and easy-to-use imaging—resonant and broadband antenna coupled ultrasensitive titanium-based—dedicated to accurately adjust and control spatial mode profiles without additional focusing optical components of weak power THz sources. Versatile operation of the devices is shown using different kinds of THz—electronic multiplier sources, optical THz mixer-based frequency domain and femtosecond optoelectronic THz time-domain spectrometers as well as optically pumped molecular THz laser. Features of the microbolometers within 0.15–0.6 THz range are exposed and discussed, their ability to detect spatial mode profiles beyond the antennas resonances, up to 2.52 THz, are explored. Polarization-sensitive mode control possibilities are examined in details. The suitability of the resonant antenna-coupled microbolometers to resolve low-absorbing objects at 0.3 THz is revealed via direct, dark field and phase contrast imaging techniques as well.


1989 ◽  
Vol 109 (4) ◽  
pp. 1711-1723 ◽  
Author(s):  
M S Tilney ◽  
L G Tilney ◽  
R E Stephens ◽  
C Merte ◽  
D Drenckhahn ◽  
...  

The sensory epithelium of the chick cochlea contains only two cell types, hair cells and supporting cells. We developed methods to rapidly dissect out the sensory epithelium and to prepare a detergent-extracted cytoskeleton. High salt treatment of the cytoskeleton leaves a "hair border", containing actin filament bundles of the stereocilia still attached to the cuticular plate. On SDS-PAGE stained with silver the intact epithelium is seen to contain a large number of bands, the most prominent of which are calbindin and actin. Detergent extraction solubilizes most of the proteins including calbindin. On immunoblots antibodies prepared against fimbrin from chicken intestinal epithelial cells cross react with the 57- and 65-kD bands present in the sensory epithelium and the cytoskeleton. It is probable that the 57-kD is a proteolytic fragment of the 65-kD protein. Preparations of stereocilia attached to the overlying tectorial membrane contain the 57- and 65-kD bands. A 400-kD band is present in the cuticular plate. By immunofluorescence, fimbrin is detected in stereocilia but not in the hair borders after salt extraction. The prominent 125 A transverse stripping pattern characteristic of the actin cross-bridges in a bundle is also absent in hair borders suggesting fimbrin as the component that gives rise to the transverse stripes. Because the actin filaments in the stereocilia of hair borders still remain as compact bundles, albeit very disordered, there must be an additional uncharacterized protein besides fimbrin that cross-links the actin filaments together.


1994 ◽  
Vol 75 (1-2) ◽  
pp. 81-92 ◽  
Author(s):  
H.M. Sobkowicz ◽  
S.M. Slapnick
Keyword(s):  

Author(s):  
Robert Adams ◽  
Jinjiang Xiao ◽  
Michael Cross ◽  
Max Deffenbaugh

Switched reluctance motors may be advantageous when used as the primary motor for an electric submersible pump system.  They are less susceptible to jamming failures due to their high starting torque and ability to reverse direction.  Driving these motors requires well-timed pulse waveforms and precise control of the motor based on its rotational position.  In general, voltage-based sensing and control systems at the surface see highly unpredictable waveforms with excessive ringing behaviour due to the impedance characteristics of the long cabling between the surface controller and the downhole motor system.  In this work, a system is detailed which monitors the current waveforms on the motor coil excitation conductors at the surface as a source of motor performance feedback and control.  State-space modelling of the system shows stable current waveforms at the surface controller for both short and long interconnect cable systems.  A laboratory demonstration of the surface controller, interconnect cabling, and motor system is shows excellent agreement with the current and voltage waveforms predicted by the state-space system model.


2008 ◽  
Vol 99 (5) ◽  
pp. 2183-2193 ◽  
Author(s):  
Lisa Grant ◽  
Paul Fuchs

Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37°C, the calcium currents of immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.


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