Journal articles: 'Stereocilin'

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Avan, Paul, Sébastien Le Gal, Vincent Michel, Typhaine Dupont, Jean-Pierre Hardelin, Christine Petit, and Elisabeth Verpy. "Otogelin, otogelin-like, and stereocilin form links connecting outer hair cell stereocilia to each other and the tectorial membrane." Proceedings of the National Academy of Sciences 116, no. 51 (November 27, 2019): 25948–57. http://dx.doi.org/10.1073/pnas.1902781116.

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The function of outer hair cells (OHCs), the mechanical actuators of the cochlea, involves the anchoring of their tallest stereocilia in the tectorial membrane (TM), an acellular structure overlying the sensory epithelium. Otogelin and otogelin-like are TM proteins related to secreted epithelial mucins. Defects in either cause the DFNB18B and DFNB84B genetic forms of deafness, respectively, both characterized by congenital mild-to-moderate hearing impairment. We show here that mutant mice lacking otogelin or otogelin-like have a marked OHC dysfunction, with almost no acoustic distortion products despite the persistence of some mechanoelectrical transduction. In both mutants, these cells lack the horizontal top connectors, which are fibrous links joining adjacent stereocilia, and the TM-attachment crowns coupling the tallest stereocilia to the TM. These defects are consistent with the previously unrecognized presence of otogelin and otogelin-like in the OHC hair bundle. The defective hair bundle cohesiveness and the absence of stereociliary imprints in the TM observed in these mice have also been observed in mutant mice lacking stereocilin, a model of the DFNB16 genetic form of deafness, also characterized by congenital mild-to-moderate hearing impairment. We show that the localizations of stereocilin, otogelin, and otogelin-like in the hair bundle are interdependent, indicating that these proteins interact to form the horizontal top connectors and the TM-attachment crowns. We therefore suggest that these 2 OHC-specific structures have shared mechanical properties mediating reaction forces to sound-induced shearing motion and contributing to the coordinated displacement of stereocilia.

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Cartagena-Rivera, Alexander X., Sébastien Le Gal, Kerianne Richards, Elisabeth Verpy, and Richard S. Chadwick. "Cochlear outer hair cell horizontal top connectors mediate mature stereocilia bundle mechanics." Science Advances 5, no. 2 (February 2019): eaat9934. http://dx.doi.org/10.1126/sciadv.aat9934.

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Outer hair cell (OHC) stereocilia bundle deflection opens mechanoelectrical transduction channels at the tips of the stereocilia from the middle and short rows, while bundle cohesion is maintained owing to the presence of horizontal top connectors. Here, we used a quantitative noncontact atomic force microscopy method to investigate stereocilia bundle stiffness and damping, when stimulated at acoustic frequencies and nanometer distances from the bundle. Stereocilia bundle mechanics were determined in stereocilin-deficient mice lacking top connectors and with detached tectorial membrane (Strc−/−/Tecta−/− double knockout) and heterozygous littermate controls (Strc+/−/Tecta−/−). A substantial decrease in bundle stiffness and damping by ~60 and ~74% on postnatal days P13 to P15 was observed when top connectors were absent. Additionally, we followed bundle mechanics during OHC top connectors development between P9 and P15 and quantified the observed increase in OHC bundle stiffness and damping in Strc+/−/Tecta−/− mice while no significant change was detected in Strc−/−/Tecta−/− animals.

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Mandelker, Diana, Sami S. Amr, Trevor Pugh, Sivakumar Gowrisankar, Rimma Shakhbatyan, Elizabeth Duffy, Mark Bowser, et al. "Comprehensive Diagnostic Testing for Stereocilin." Journal of Molecular Diagnostics 16, no. 6 (November 2014): 639–47. http://dx.doi.org/10.1016/j.jmoldx.2014.06.003.

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Verpy, Elisabeth, Michel Leibovici, Nicolas Michalski, Richard J. Goodyear, Carine Houdon, Dominique Weil, Guy P. Richardson, and Christine Petit. "Stereocilin connects outer hair cell stereocilia to one another and to the tectorial membrane." Journal of Comparative Neurology 519, no. 2 (December 16, 2010): 194–210. http://dx.doi.org/10.1002/cne.22509.

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Han, Woongsu, Jeong-Oh Shin, Ji-Hyun Ma, Hyehyun Min, Jinsei Jung, Jinu Lee, Un-Kyung Kim, et al. "Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells." Proceedings of the National Academy of Sciences 117, no. 20 (May 1, 2020): 11109–17. http://dx.doi.org/10.1073/pnas.1920229117.

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Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.

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Verpy, Elisabeth, Dominique Weil, Michel Leibovici, Richard J. Goodyear, Ghislaine Hamard, Carine Houdon, Gaelle M. Lefèvre, et al. "Stereocilin-deficient mice reveal the origin of cochlear waveform distortions." Nature 456, no. 7219 (October 8, 2008): 255–58. http://dx.doi.org/10.1038/nature07380.

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Frykholm, Carina, Joakim Klar, Tatjana Tomanovic, Adam Ameur, and Niklas Dahl. "Stereocilin gene variants associated with episodic vertigo: expansion of the DFNB16 phenotype." European Journal of Human Genetics 26, no. 12 (September 24, 2018): 1871–74. http://dx.doi.org/10.1038/s41431-018-0256-6.

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Pacentine, Itallia, Paroma Chatterjee, and Peter G. Barr-Gillespie. "Stereocilia Rootlets: Actin-Based Structures That Are Essential for Structural Stability of the Hair Bundle." International Journal of Molecular Sciences 21, no. 1 (January 3, 2020): 324. http://dx.doi.org/10.3390/ijms21010324.

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Sensory hair cells of the inner ear rely on the hair bundle, a cluster of actin-filled stereocilia, to transduce auditory and vestibular stimuli into electrical impulses. Because they are long and thin projections, stereocilia are most prone to damage at the point where they insert into the hair cell’s soma. Moreover, this is the site of stereocilia pivoting, the mechanical movement that induces transduction, which additionally weakens this area mechanically. To bolster this fragile area, hair cells construct a dense core called the rootlet at the base of each stereocilium, which extends down into the actin meshwork of the cuticular plate and firmly anchors the stereocilium. Rootlets are constructed with tightly packed actin filaments that extend from stereocilia actin filaments which are wrapped with TRIOBP; in addition, many other proteins contribute to the rootlet and its associated structures. Rootlets allow stereocilia to sustain innumerable deflections over their lifetimes and exemplify the unique manner in which sensory hair cells exploit actin and its associated proteins to carry out the function of mechanotransduction.

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Sathyanarayana, Bangalore K., Yoonsoo Hahn, Manish S. Patankar, Ira Pastan, and Byungkook Lee. "Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats." BMC Structural Biology 9, no. 1 (2009): 1. http://dx.doi.org/10.1186/1472-6807-9-1.

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Avenarius, Matthew R., Jocelyn F. Krey, Rachel A. Dumont, Clive P. Morgan, Connor B. Benson, Sarath Vijayakumar, Christopher L. Cunningham, et al. "Heterodimeric capping protein is required for stereocilia length and width regulation." Journal of Cell Biology 216, no. 11 (September 12, 2017): 3861–81. http://dx.doi.org/10.1083/jcb.201704171.

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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.

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Tilney, L. G., and M. S. Tilney. "The actin filament content of hair cells of the bird cochlea is nearly constant even though the length, width, and number of stereocilia vary depending on the hair cell location." Journal of Cell Biology 107, no. 6 (December 1, 1988): 2563–74. http://dx.doi.org/10.1083/jcb.107.6.2563.

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By direct counts off scanning electron micrographs, we determined the number of stereocilia per hair cell of the chicken cochlea as a function of the position of the hair cell on the cochlea. Micrographs of thin cross sections of stereociliary bundles located at known positions on the cochlea were enlarged and the total number of actin filaments per stereocilium was counted and recorded. By comparing the counts of filament number with measurements of actin filament bundle width of the same stereocilium, we were able to relate actin filament bundle width to filament number with an error margin (r2) of 16%. Combining this data with data already published or in the process of publication from our laboratory on the length and width of stereocilia, we were able to calculate the total length of actin filaments present in stereociliary bundles of hair cells located at a variety of positions on the cochlea. We found that stereociliary bundles of hair cells contain 80,000-98,000 micron of actin filament, i.e., the concentration of actin is constant in all hair cells with a range of values that is less than our error in measurement and/or biological variation, the greatest variation being in relating the diameters of the stereocilia to filament number. We also calculated the membrane surface needed to cover the stereocilia of hair cells located throughout the cochlea. The values (172-192 micron 2) are also constant. The implications of our observation that the total amount of actin is constant even though the length, width, and number of stereocilia per hair cell vary are discussed.

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Jeffries, David J., James O. Pickles, Michael P. Osborne, Peter H. Rhys-Evans, and Spiro D. Comis. "Crosslinks between stereocilia in hair cells of the human and guinea pig vestibular labyrinth." Journal of Laryngology & Otology 100, no. 12 (December 1986): 1367–74. http://dx.doi.org/10.1017/s002221510010115x.

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AbstractThe saccules and ampullae of the semicircular canals from human and guinea pig temporal bones were fixed in glutaraldehyde without osmium. Crosslinks were seen between stereocilia of the vestibular hair cells, similar to those previously demonstrated in the guinea pig, although an additional set of crosslinks was displayed: first, horizontal crosslinks were seen between adjacent stereocilia, occupying most of the length of the hair bundle; secondly, a single upward-pointing link ran from the apex of each shorter stereocilium into the shaft of the adjacent taller ster-eocilium; thirdly, an extensive array of horizontal links were demonstrated between stereocilia close to their insertion into the cuticular plate. We suggest that these basal crosslinks support the long vestibular stereocilia rendering them more rigid, and that the upwind pointing crosslinks are responsible for the initiation of sensory transduction.

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Rhys Evans, Peter H., Spiro D. Comis, Michael P. Osborne, James O. Pickles, and David J. R. Jeffries. "Cross-links between stereocilia in the human organ of Corti." Journal of Laryngology & Otology 99, no. 1 (January 1985): 11–20. http://dx.doi.org/10.1017/s0022215100096237.

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AbstractHuman cochleae were fixed in glutaraldehyde, without the use of osmium. Crosslinks were seen between the stereocilia, similar to those we have previously reported for the guinea pig: first, stereocilia of the same row on each hair cell were joined by horizontally-running links; secondly, the shorter stereocilia had pointed tips, each giving rise to a single, vertically-pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link is involved in sensory transduction. The links were sparser than had been seen in the guinea pig which may be a reflection of the vulnerability of the links to nonoptimal fixation, and the greater difficulty in producing good fixation in human specimens.

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Prosser, Haydn M., Agnieszka K. Rzadzinska, Karen P. Steel, and Allan Bradley. "Mosaic Complementation Demonstrates a Regulatory Role for Myosin VIIa in Actin Dynamics of Stereocilia." Molecular and Cellular Biology 28, no. 5 (December 26, 2007): 1702–12. http://dx.doi.org/10.1128/mcb.01282-07.

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ABSTRACT We have developed a bacterial artificial chromosome transgenesis approach that allowed the expression of myosin VIIa from the mouse X chromosome. We demonstrated the complementation of the Myo7a null mutant phenotype producing a fine mosaic of two types of sensory hair cells within inner ear epithelia of hemizygous transgenic females due to X inactivation. Direct comparisons between neighboring auditory hair cells that were different only with respect to myosin VIIa expression revealed that mutant stereocilia are significantly longer than those of their complemented counterparts. Myosin VIIa-deficient hair cells showed an abnormally persistent tip localization of whirlin, a protein directly linked to elongation of stereocilia, in stereocilia. Furthermore, myosin VIIa localized at the tips of all abnormally short stereocilia of mice deficient for either myosin XVa or whirlin. Our results strongly suggest that myosin VIIa regulates the establishment of a setpoint for stereocilium heights, and this novel role may influence their normal staircase-like arrangement within a bundle.

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Xu, Xu, Wen-Kai Ma, and Wen-Juan Yao. "Dynamic study of tip-link tension and stereocilia motion in cochlea." Acta Physica Sinica 71, no. 4 (2022): 048705. http://dx.doi.org/10.7498/aps.71.20211105.

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Explanation of cochlear active acoustic amplification mechanism has been an unsolved medical problem. This mechanism is closely related to the motion of the stereocilia at the top of the outer hair cells in the cochlea. The motion of stereocilia is regulated by the tip-link tension and the fluid force of the lymph fluid. Therefore, studying the tip-link tension during the motion of stereocilia is an important part of the explanation of the cochlea's active sensory sound amplification mechanism. Most of previous studies regarded the stereocilia as rigid bodies, and ignored the influence of shaft bending when studying the mechanical properties of hair bundle. Most of the researches on elastic stereocilia used the finite element simulation, or simplified the model by ignoring the fluid-solid coupling with lymph fluid, or considered only static loading. Based on the Poiseuille flow combined with the distributed parameter model, the analytical solution of the elastic motion of stereocilia is derived in this work. The dynamic response of the stereocilia under the shear force of the tectorial membrane and the change law of tip-link tension are studied. The shaft bending produces a nonlinear accumulation of displacement at the height of the stereocilia. The higher the stereocilia, the more obvious the accumulation effect is. Under the action of dynamic load, the shaft bending contributes most to the displacement response in the tall stereocilium, and this contribution is easily affected by frequency change. Under low frequency load, the displacement response of tall stereocilium comes mainly from the root deflection. At high frequency, the shaft bending increases significantly, and the displacement response is produced by the combination of shaft bending and root deflection. The change of F-actin content in the cochlea exposed to noise would affect the stereocilia stiffness. In this paper, it is found that the decrease of stereociliary Young's modulus will increase the peak value of normalized tension and reduce its peak frequency, and the amplitude of normalized tension will increase under the low frequency shear load. Since the tip-link is connected to an ion channel, the change of normalized tension will affect the probability of ion channels opening, change the ability of cochlea to perceive the sound of corresponding frequency, and then affect the frequency selectivity of hair bundle. Therefore, previous studies of stereocilia regarded as rigid bodies underestimated the response of the cochlea to low-frequency acoustic signals. This model accurately describes the law of tip-link tension and provides a corresponding theoretical explanation for hearing impairment caused by noise environment. Previous experiments have shown that the lymphatic viscous resistance has little effect on the deflection of stereocilia. In this paper, when the viscous resistance is ignored, the tip-link tension changes very little, and when the pressure between the stereocilia is ignored, the tip-link tension changes significantly and the resonance peak of <inline-formula><tex-math id="M4">\begin{document}$ {f_2} $\end{document}</tex-math><alternatives><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20211105_M4.jpg"/><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20211105_M4.png"/></alternatives></inline-formula> disappears. Therefore, lymphatic fluid regulates the resonance properties of the tip-link tension by creating the pressure between the stereocilia. The presence of lymphatics is essential for generating the frequency characteristics of the hair bundle. In the low frequency domain, the motion of stereocilia is regulated mainly by tip-link, and in the high frequency domain, it is regulated mainly by lymphatic pressure.

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Francey, Lauren J., Laura K. Conlin, Hanna E. Kadesch, Dinah Clark, Donna Berrodin, Yi Sun, Joe Glessner, et al. "Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major contributor to pediatric bilateral sensorineural hearing impairment." American Journal of Medical Genetics Part A 158A, no. 2 (December 6, 2011): 298–308. http://dx.doi.org/10.1002/ajmg.a.34391.

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Domínguez-Ruiz, María, Laura Ruiz-Palmero, Paula I. Buonfiglio, Irene García-Vaquero, Elena Gómez-Rosas, Marina Goñi, Manuela Villamar, et al. "Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects." Biomedicines 11, no. 11 (October 31, 2023): 2943. http://dx.doi.org/10.3390/biomedicines11112943.

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Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.

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Peixoto de Barcelos, Isabella, Dong Li, Deborah Watson, Elizabeth M. McCormick, Lisa Elden, Thomas S. Aleman, Erin C. O’Neil, Marni J. Falk, and Hakon Hakonarson. "Multiple Independent Gene Disorders Causing Bardet–Biedl Syndrome, Congenital Hypothyroidism, and Hearing Loss in a Single Indian Patient." Brain Sciences 13, no. 8 (August 16, 2023): 1210. http://dx.doi.org/10.3390/brainsci13081210.

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We report a 20-year-old, female, adopted Indian patient with over 662 Mb regions of homozy-gosity who presented with intellectual disability, ataxia, schizophrenia, retinal dystrophy, moder-ate-to-severe progressive sensorineural hearing loss (SNHL), congenital hypothyroidism, cleft mi-tral valve with mild mitral valve regurgitation, and dysmorphic features. Exome analysis first on a clinical basis and subsequently on research reanalysis uncovered pathogenic variants in three nu-clear genes following two modes of inheritance that were causal to her complex phenotype. These included (1) compound heterozygous variants in BBS6 potentially causative for Bardet–Biedl syn-drome 6; (2) a homozygous, known pathogenic variant in the stereocilin (STRC) gene associated with nonsyndromic deafness; and (3) a homozygous variant in dual oxidase 2 (DUOX2) gene asso-ciated with congenital hypothyroidism. A variant of uncertain significance was identified in a fourth gene, troponin T2 (TNNT2), associated with cardiomyopathy but not the cleft mitral valve, with mild mitral regurgitation seen in this case. This patient was the product of an apparent first-degree relationship, explaining the multiple independent inherited findings. This case high-lights the need to carefully evaluate multiple independent genetic etiologies for complex pheno-types, particularly in the case of consanguinity, rather than presuming unexplained features are expansions of known gene disorders.

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Petit, Christine, and Paul Avan. "Stereocilin in top-connectors is a key element ensuring waveform distortion and suppressive masking, necessary for speech intelligibility and hearing in noise." La lettre du Collège de France, no. 4 (June 1, 2009): 45–47. http://dx.doi.org/10.4000/lettre-cdf.775.

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Harrison, R. V., R. J. Mount, P. White, and N. Fukushima. "Histological evaluation of cochlear hair cell damage from noise-induced hearing loss in chinchillas." Proceedings, annual meeting, Electron Microscopy Society of America 48, no. 3 (August 12, 1990): 332–33. http://dx.doi.org/10.1017/s0424820100159217.

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In studies which attempt to define the influence of various factors on recovery of hair cell integrity after acoustic trauma, an experimental and a control ear which initially have equal degrees of damage are required. With in a group of animals receiving an identical level of acoustic trauma there is more symmetry between the ears of each individual, in respect to function, than between animals. Figure 1 illustrates this, left and right cochlear evoked potential (CAP) audiograms are shown for two chinchillas receiving identical trauma. For this reason the contralateral ear is used as control.To compliment such functional evaluations we have devised a scoring system, based on the condition of hair cell stereocilia as revealed by scanning electron microscopy, which permits total stereociliar damage to be expressed numerically. This quantification permits correlation of the degree of structural pathology with functional changes. In this paper wereport experiments to verify the symmetry of stereociliar integrity between two ears, both for normal (non-exposed) animals and chinchillas in which each ear has received identical noise trauma.

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YAO, WENJUAN, and YIQIANG CHEN. "NUMERICAL SIMULATION ON THE MECHANICAL BEHAVIOR OF OUTER STEREOCILIA IN CORTI." Journal of Mechanics in Medicine and Biology 17, no. 03 (September 23, 2016): 1750045. http://dx.doi.org/10.1142/s0219519417500452.

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In this paper, a two-dimensional model of the organ of Corti (OC) which includes basilar membrane (BM), tectorial membrane (TM), inner and outer hair cells and reticular lamina (RL) is established by Comsol. Based on experimental data that sinusoidal excitation was applied on the pectinate zone of the BM, the incentives are added to the corresponding position of the model. Transient analysis is made and the displacement of six different positions is achieved. The results are in good agreement with experimental data, which confirms the validity of the FE model. Based on time-domain and frequency-domain analysis, the relative motion between stereocilia and TM and RL is studied under sinusoidal excitation. The results show that, under time-domain analysis, the whole trend of relative displacement and velocity difference of Inner is similar to that of Outer, while there is little different when comparing with Middle. The relative velocity difference of Middle and Inner lag behind Outer with roughly 0.01[Formula: see text]s. Under frequency-domain analysis, at characteristic frequency, the deviation of each stereocilium is the largest. In the meantime, the frequency that the maximum value of outer stereocilia achieved is different. This new finding may cause the difference of lateral vibration of BM and indicate the frequency sensitivity of BM.

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Drenckhahn, D., K. Engel, D. Höfer, C. Merte, L. Tilney, and M. Tilney. "Three different actin filament assemblies occur in every hair cell: each contains a specific actin crosslinking protein." Journal of Cell Biology 112, no. 4 (February 15, 1991): 641–51. http://dx.doi.org/10.1083/jcb.112.4.641.

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The apex of hair cells of the chicken auditory organ contains three different kinds of assemblies of actin filaments in close spatial proximity. These are (a) paracrystals of actin filaments with identical polarity in stereocilia, (b) a dense gellike meshwork of actin filaments forming the cuticular plate, and (c) a bundle of parallel actin filaments with mixed polarities that constitute the circumferential filament belt attached to the cytoplasmic aspect of the zonula adhaerens (ZA). Each different supramolecular assembly of actin filaments contains a specific actin filament cross-linking protein which is unique to that particular assembly. Thus fimbrin appears to be responsible for paracrystallin packing of actin filaments in stereocillia; an isoform of spectrin resides in the cuticular plate where it forms the whisker-like crossbridges, and alpha actinin is the actin crosslinking protein of the circumferential ZA bundle. Tropomyosin, which stabilizes actin filaments, is present in all the actin filament assemblies except for the stereocilia. Another striking finding was that myosin appears to be absent from the ZA ring and cuticular plate of hair cells although present in the ZA ring of supporting cells. The abundance of myosin in the ZA ring of the surrounding supporting cells means that it may be important in forming a supporting tensile cellular framework in which the hair cells are inserted.

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Amr, Sami S., Elissa Murphy, Elizabeth Duffy, Rojeen Niazi, Jorune Balciuniene, Minjie Luo, Heidi L. Rehm, and Ahmad N. Abou Tayoun. "Allele-Specific Droplet Digital PCR Combined with a Next-Generation Sequencing-Based Algorithm for Diagnostic Copy Number Analysis in Genes with High Homology: Proof of Concept Using Stereocilin." Clinical Chemistry 64, no. 4 (April 1, 2018): 705–14. http://dx.doi.org/10.1373/clinchem.2017.280685.

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Abstract BACKGROUND Copy number variants (CNVs) can substantially contribute to the pathogenic variant spectrum in several disease genes. The detection of this type of variant is complicated in genes with high homology to other genomic sequences, yet such genomics regions are more likely to lead to CNVs, making it critical to address detection in these settings. METHODS We developed a copy number analysis approach for high homology genes/regions that consisted of next-generation sequencing (NGS)-based dosage analysis accompanied by allele-specific droplet digital PCR (ddPCR) confirmatory testing. We applied this approach to copy number analysis in STRC, a gene with 98.9% homology to a nonfunctional pseudogene, pSTRC, and characterized its accuracy in detecting different copy number states by use of known samples. RESULTS Using a cohort of 517 patients with hearing loss, we prospectively demonstrated the clinical utility of the approach, which contributed 30 of the 122 total positives (6%) to the diagnostic yield, increasing the overall yield from 17.6% to 23.6%. Positive STRC genotypes included homozygous (n = 15) or compound heterozygous (n = 8) deletions, or heterozygous deletions in trans with pathogenic sequence variants (n = 7). Finally, this approach limited ddPCR testing to cases with NGS copy number findings, thus markedly reducing the number of costly and laborious, albeit specific, ddPCR tests. CONCLUSIONS NGS-based CNV detection followed by allele-specific ddPCR confirmatory testing is a reliable and affordable approach for copy number analysis in medically relevant genes with homology issues.

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Roy, Pallabi, and Benjamin J. Perrin. "The stable actin core of mechanosensory stereocilia features continuous turnover of actin cross-linkers." Molecular Biology of the Cell 29, no. 15 (August 2018): 1856–65. http://dx.doi.org/10.1091/mbc.e18-03-0196.

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Stereocilia are mechanosensitive protrusions on the surfaces of sensory hair cells in the inner ear that detect sound, gravity, and head movement. Their cores are composed of parallel actin filaments that are cross-linked and stabilized by several actin-binding proteins, including fascin-2, plastin-1, espin, and XIRP2. The actin filaments are the most stable known, with actin turnover primarily occurring at the stereocilia tips. While stereocilia actin dynamics has been well studied, little is known about the behavior of the actin cross-linking proteins, which are the most abundant type of protein in stereocilia after actin and are critical for stereocilia morphogenesis and maintenance. Here, we developed a novel transgenic mouse to monitor EGFP-fascin-2 incorporation . In contrast to actin, EGFP-fascin-2 readily enters the stereocilia core. We also compared the effect of EGFP-fascin-2 expression on developing and mature stereocilia. When it was induced during hair cell development, we observed increases in both stereocilia length and width. Interestingly, stereocilia size was not affected when EGFP-fascin-2 was induced in adult stereocilia. Regardless of the time of induction, EGFP-fascin-2 displaced both espin and plastin-1 from stereocilia. Altering the actin cross-linker composition, even as the actin filaments exhibit little to no turnover, provides a mechanism for ongoing remodeling and repair important for stereocilia homeostasis.

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Krey, Jocelyn F., Evan S. Krystofiak, Rachel A. Dumont, Sarath Vijayakumar, Dongseok Choi, Francisco Rivero, Bechara Kachar, Sherri M. Jones, and Peter G. Barr-Gillespie. "Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid." Journal of Cell Biology 215, no. 4 (November 3, 2016): 467–82. http://dx.doi.org/10.1083/jcb.201606036.

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With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.

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Tilney, L. G., D. A. Cotanche, and M. S. Tilney. "Actin filaments, stereocilia and hair cells of the bird cochlea. VI. How the number and arrangement of stereocilia are determined." Development 116, no. 1 (September 1, 1992): 213–26. http://dx.doi.org/10.1242/dev.116.1.213.

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Beginning in 8-day embryos, stereocilia sprout from the apical surface of hair cells apparently at random. As the embryo continues to develop, the number of stereocilia increases. By 10 1/2 days the number is approximately the same as that encountered extending from mature hair cells at the same relative positions in the adult cochlea. Surprisingly, over the next 2–3 days the number of stereocilia continues to increase so that hair cells in a 12-day embryo have 1 1/2 to 2 times as many stereocilia as in adult hair cells. In short, there is an overshoot in stereociliary number. During the same period in which stereocilia are formed (9-12 days) the apical surface of each hair cell is filled with closely packed stereocilia; thus the surface area is proportional to the number of stereocilia present per hair cell, as if these features were coupled. The staircase begins to form in a 10-day embryo, with what will be the tallest row beginning to elongate first and gradually row after row begins to elongate by incorporation of stereocilia at the foot of the staircase. Extracellular connections or tip linkages appear as the stereocilia become incorporated into the staircase. After a diminutive staircase has formed, eg. in a 12-day embryo, the remaining stereocilia located at the foot of the staircase begin to be reabsorbed, a process that occurs during the next few days. We conclude that the hair cell determines the number of stereocilia to form by filling up the available apical surface area with stereocilia and then, by cropping back those that are not stabilized by extracellular linkages, arrives at the appropriate number. Furthermore, the stereociliary pattern, which changes from having a round cross-sectional profile to a rectangular one, is generated by these same linkages which lock the stereocilia into a precise pattern. As this pattern is established, we envision that the stereocilia flow over the apical surface until frozen in place by the formation of the cuticular plate in the apical cell cytoplasm.

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Rzadzinska, Agnieszka K., Mark E. Schneider, Caroline Davies, Gavin P. Riordan, and Bechara Kachar. "An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal." Journal of Cell Biology 164, no. 6 (March 15, 2004): 887–97. http://dx.doi.org/10.1083/jcb.200310055.

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We have previously shown that the seemingly static paracrystalline actin core of hair cell stereocilia undergoes continuous turnover. Here, we used the same approach of transfecting hair cells with actin–green fluorescent protein (GFP) and espin-GFP to characterize the turnover process. Actin and espin are incorporated at the paracrystal tip and flow rearwards at the same rate. The flux rates (∼0.002–0.04 actin subunits s−1) were proportional to the stereocilia length so that the entire staircase stereocilia bundle was turned over synchronously. Cytochalasin D caused stereocilia to shorten at rates matching paracrystal turnover. Myosins VI and VIIa were localized alongside the actin paracrystal, whereas myosin XVa was observed at the tips at levels proportional to stereocilia lengths. Electron microscopy analysis of the abnormally short stereocilia in the shaker 2 mice did not show the characteristic tip density. We argue that actin renewal in the paracrystal follows a treadmill mechanism, which, together with the myosins, dynamically shapes the functional architecture of the stereocilia bundle.

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Krey, Jocelyn F., Paroma Chatterjee, Julia Halford, Christopher L. Cunningham, Benjamin J. Perrin, and Peter G. Barr-Gillespie. "Control of stereocilia length during development of hair bundles." PLOS Biology 21, no. 4 (April 3, 2023): e3001964. http://dx.doi.org/10.1371/journal.pbio.3001964.

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Assembly of the hair bundle, the sensory organelle of the inner ear, depends on differential growth of actin-based stereocilia. Separate rows of stereocilia, labeled 1 through 3 from tallest to shortest, lengthen or shorten during discrete time intervals during development. We used lattice structured illumination microscopy and surface rendering to measure dimensions of stereocilia from mouse apical inner hair cells during early postnatal development; these measurements revealed a sharp transition at postnatal day 8 between stage III (row 1 and 2 widening; row 2 shortening) and stage IV (final row 1 lengthening and widening). Tip proteins that determine row 1 lengthening did not accumulate simultaneously during stages III and IV; while the actin-bundling protein EPS8 peaked at the end of stage III, GNAI3 peaked several days later—in early stage IV—and GPSM2 peaked near the end of stage IV. To establish the contributions of key macromolecular assemblies to bundle structure, we examined mouse mutants that eliminated tip links (Cdh23v2J or Pcdh15av3J), transduction channels (TmieKO), or the row 1 tip complex (Myo15ash2). Cdh23v2J/v2J and Pcdh15av3J/av3J bundles had adjacent stereocilia in the same row that were not matched in length, revealing that a major role of these cadherins is to synchronize lengths of side-by-side stereocilia. Use of the tip-link mutants also allowed us to distinguish the role of transduction from effects of transduction proteins themselves. While levels of GNAI3 and GPSM2, which stimulate stereocilia elongation, were greatly attenuated at the tips of TmieKO/KO row 1 stereocilia, they accumulated normally in Cdh23v2J/v2J and Pcdh15av3J/av3J stereocilia. These results reinforced the suggestion that the transduction proteins themselves facilitate localization of proteins in the row 1 complex. By contrast, EPS8 concentrates at tips of all TmieKO/KO, Cdh23v2J/v2J, and Pcdh15av3J/av3J stereocilia, correlating with the less polarized distribution of stereocilia lengths in these bundles. These latter results indicated that in wild-type hair cells, the transduction complex prevents accumulation of EPS8 at the tips of shorter stereocilia, causing them to shrink (rows 2 and 3) or disappear (row 4 and microvilli). Reduced rhodamine-actin labeling at row 2 stereocilia tips of tip-link and transduction mutants suggests that transduction’s role is to destabilize actin filaments there. These results suggest that regulation of stereocilia length occurs through EPS8 and that CDH23 and PCDH15 regulate stereocilia lengthening beyond their role in gating mechanotransduction channels.

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Kitajiri, Shin-ichiro, Kanehisa Fukumoto, Masaki Hata, Hiroyuki Sasaki, Tatsuya Katsuno, Takayuki Nakagawa, Juichi Ito, Shoichiro Tsukita, and Sachiko Tsukita. "Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia." Journal of Cell Biology 166, no. 4 (August 16, 2004): 559–70. http://dx.doi.org/10.1083/jcb.200402007.

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Ezrin/radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that radixin-deficient (Rdx−/−) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (∼2 wk), in the cochlea and vestibule of Rdx−/− mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx−/− mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx−/− mice. Thus, we concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx−/− mice, ezrin appeared to compensate for radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.

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Lelli, Andrea, Vincent Michel, Jacques Boutet de Monvel, Matteo Cortese, Montserrat Bosch-Grau, Asadollah Aghaie, Isabelle Perfettini, et al. "Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth." Journal of Cell Biology 212, no. 2 (January 11, 2016): 231–44. http://dx.doi.org/10.1083/jcb.201509017.

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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.

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Moravec, W. J., and E. H. Peterson. "Differences Between Stereocilia Numbers on Type I and Type II Vestibular Hair Cells." Journal of Neurophysiology 92, no. 5 (November 2004): 3153–60. http://dx.doi.org/10.1152/jn.00428.2004.

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A major outstanding goal of vestibular neuroscience is to understand the distinctive functional roles of type I and type II hair cells. One important question is whether these two hair cell types differ in bundle structure. To address this, we have developed methods to characterize stereocilia numbers on identified type I and type II hair cells in the utricle of a turtle, Trachemys scripta. Our data indicate that type I hair cells, which occur only in the striola, average 95.9 ±16.73 (SD) stereocilia per bundle. In contrast, striolar type II hair cells have 59.9 ± 8.98 stereocilia, and type II hair cells in the adjacent extrastriola average 44.8 ± 10.82 stereocilia. Thus type I hair cells have the highest stereocilia counts in the utricle. These results provide the first direct evidence that type I hair cells have significantly more stereocilia than type II hair cells, and they suggest that the two hair cell types may differ in bundle mechanics and peak mechanoelectric transduction currents.

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Corwin, Jeffrey T. "Development and self-repair in hair cell epithelia." Proceedings, annual meeting, Electron Microscopy Society of America 47 (August 6, 1989): 792–93. http://dx.doi.org/10.1017/s0424820100155931.

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This presentation will attempt to explain current understanding of the cellular mechanisms of normal hair cell development and the mechanisms of hair cell regeneration. Hair cells are the mechanoreceptors that transduce sound and balance stimulation of the ear and water current stimulation of the lateral line organs into electrical activity that is transmitted to the brain. Hair cells have one true cilium, the kinocilium, and 30 to 200 or more stereocilia which are modified, actin-filled microvilli, that project from the flat apical surfaces of the cells. The stereocilia are arrayed across each cell in an “organ pipe” arrangement, with a row of short stereocilia at one end and rows of increasingly taller stereocilia proceeding from that row toward the single eccentrically positioned kinocilium. That asymmetrical surface structure defines the functional polarity of each hair cell, because stimuli that mechanically bend the stereocilia array in the direction of its tall end cause a decrease in the transmembrane potential of the hair cell and increased exocytotic release of neurotransmitter from vesicles at tonically active synaptic sites in the subnuclear region. In that way the appropriately directed bending of the stereocilia causes excitation of neurons that conduct action potentials to the brain. Bending of the stereocilia in the opposite direction causes hyperpolarization of the hair cell, reduction in the exocytosis of neurotransmitter, and a resulting decrease in the frequency of action potentials conducted to the brain.In most mature organs the orientations of the stereocilia arrays of the hair cells are aligned throughout the epithelia. However, during early development of these cells their cilia bundles are oriented in a nearly random distribution. As the cells differentiate their cilia arrays grow taller and reorient, so that neighbors come into alignment. In some epithelia, such as the auditory epithelium in the cochlea of the chicken, both the number and the maximum length of the stereocilia on hair cells vary systematically along gradients related to cell position in the epithelium. This pattern of sensory cell ultrastructure correlates with the high to low pitch tuning of the basilar membrane that supports the epithelium and with the tuning of the neurons that contact the individual cells. Cells at the distal end of the chicken cochlea have less than 50 stereocilia; cells at the proximal end have over 200. The stereocilia on proximal hair cells are short (<2 microns); those on distal hair cells are long (>5 microns). The reorientation of the stereocilia arrays and their location-specific differences in stereocilia number and length all become recognizable at approximately the time when synapses form between these cells and their neurons, but experiments have shown that these processes of hair cell differentiation can occur in the absence of neurons. Several hypotheses that attempt to explain the control of differentiation in hair cells will be covered

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33

Tilney, LG, MS Tilney, and DA Cotanche. "Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated." Journal of Cell Biology 106, no. 2 (February 1, 1988): 355–65. http://dx.doi.org/10.1083/jcb.106.2.355.

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The stereocilia on each hair cell are arranged into rows of ascending height, resulting in what we refer to as a "staircase-like" profile. At the proximal end of the cochlea the length of the tallest row of stereocilia in the staircase is 1.5 micron, with the shortest row only 0.3 micron. As one proceeds towards the distal end of the cochlea the length of the stereocilia progressively increases so that at the extreme distal end the length of the tallest row of the staircase is 5.5 micron and the shortest row is 2 micron. During development hair cells form their staircases in four phases of growth separated from each other by developmental time. First, stereocilia sprout from the apical surfaces of the hair cells (8-10-d embryos). Second (10-12-d embryos), what will be the longest row of the staircase begins to elongate. As the embryo gets older successive rows of stereocilia initiate elongation. Thus the staircase is set up by the sequential initiation of elongation of stereociliary rows located at increased distances from the row that began elongation. Third (12-17-d embryos), all the stereocilia in the newly formed staircase elongate until those located on the first step of the staircase have reached the prescribed length. In the final phase (17-d embryos to hatchlings) there is a progressive cessation of elongation beginning with the shortest step and followed by taller and taller rows with the tallest step stopping last. Thus, to obtain a pattern of stereocilia in rows of increasing height what transpires are progressive go signals followed by a period when all the stereocilia grow and ending with progressive stop signals. We discuss how such a sequence could be controlled.

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Strimbu, Clark Elliott, Sonal Prasad, Pierre Hakizimana, and Anders Fridberger. "Control of hearing sensitivity by tectorial membrane calcium." Proceedings of the National Academy of Sciences 116, no. 12 (March 5, 2019): 5756–64. http://dx.doi.org/10.1073/pnas.1805223116.

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When sound stimulates the stereocilia on the sensory cells in the hearing organ, Ca2+ions flow through mechanically gated ion channels. This Ca2+influx is thought to be important for ensuring that the mechanically gated channels operate within their most sensitive response region, setting the fraction of channels open at rest, and possibly for the continued maintenance of stereocilia. Since the extracellular Ca2+concentration will affect the amount of Ca2+entering during stimulation, it is important to determine the level of the ion close to the sensory cells. Using fluorescence imaging and fluorescence correlation spectroscopy, we measured the Ca2+concentration near guinea pig stereocilia in situ. Surprisingly, we found that an acellular accessory structure close to the stereocilia, the tectorial membrane, had much higher Ca2+than the surrounding fluid. Loud sounds depleted Ca2+from the tectorial membrane, and Ca2+manipulations had large effects on hair cell function. Hence, the tectorial membrane contributes to control of hearing sensitivity by influencing the ionic environment around the stereocilia.

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Liu, Bin, Junyi Liang, Wenjuan Yao, and Chun Xu. "The Potential Changes and Stereocilia Movements during the Cochlear Sound Perception Process." Mathematics 12, no. 16 (August 10, 2024): 2470. http://dx.doi.org/10.3390/math12162470.

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Sound vibrations generate electrical signals called cochlear potentials, which can reflect cochlear stereocilia movement and outer hair cells (OHC) mechanical activity. However, because the cochlear structure is delicate and complex, it is difficult for existing measurement techniques to pinpoint the origin of potentials. This limitation in measurement capability makes it difficult to fully understand the contribution of stereocilia and transduction channels to cochlear potentials. In view of this, firstly, this article obtains the stereocilia movement generated by basilar membrane (BM) vibration based on the positional relationship between the various structures of the organ Corti. Secondly, Kirchhoff’s law is used to establish an electric field model of the cochlear cavity, and the stereocilia movement is embedded in the electric field by combining the gated spring model. Finally, a force-electric coupling mathematical model of the cochlea is established. The results indicated that the resistance variation between different cavities in the cochlea leads to a sharp tuning curve. As the displacement of the BM increased, the longitudinal potential along the cochlea continued to move toward the base. The decrease in stereocilia stiffness reduced the deflection angle, thereby reducing the transduction current and lymphatic potential.

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Yao, Qingxiu, Hui Wang, Hengchao Chen, Zhuangzhuang Li, Yumeng Jiang, Zhipeng Li, Jiping Wang, et al. "Essential Role of Sptan1 in Cochlear Hair Cell Morphology and Function Via Focal Adhesion Signaling." Molecular Neurobiology 59, no. 1 (October 27, 2021): 386–404. http://dx.doi.org/10.1007/s12035-021-02551-2.

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AbstractHearing loss is the most common human sensory deficit. Hearing relies on stereocilia, inserted into the cuticular plate of hair cells (HCs), where they play an important role in the perception of sound and its transmission. Although numerous genes have been associated with hearing loss, the function of many hair cell genes has yet to be elucidated. Herein, we focused on nonerythroid spectrin αII (SPTAN1), abundant in the cuticular plate, surrounding the rootlets of stereocilia and along the plasma membrane. Interestingly, mice with HC-specific Sptan1 knockout exhibited rapid deafness, abnormal formation of stereocilia and cuticular plates, and loss of HCs from middle and apical turns of the cochlea during early postnatal stages. Additionally, Sptan1 deficiency led to the decreased spreading of House Ear Institute-Organ of Corti 1 cells, and induced abnormal formation of focal adhesions and integrin signaling in mouse HCs. Altogether, our findings highlight SPTAN1 as a critical molecule for HC stereocilia morphology and auditory function via regulation of focal adhesion signaling.

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Vélez-Ortega, A. Catalina, and Gregory I. Frolenkov. "Auditory Hair Cell Stereocilia." Hearing Journal 70, no. 11 (November 2017): 8. http://dx.doi.org/10.1097/01.hj.0000527208.28817.42.

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Boutet de Monvel, Jacques, and Christine Petit. "Wrapping up Stereocilia Rootlets." Cell 141, no. 5 (May 2010): 748–50. http://dx.doi.org/10.1016/j.cell.2010.05.022.

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Ikäheimo, Kuu, Anni Herranen, Vilma Iivanainen, Tuuli Lankinen, Antti A. Aarnisalo, Ville Sivonen, Kashyap A. Patel, et al. "MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochlea." Life Science Alliance 5, no. 2 (November 23, 2021): e202101068. http://dx.doi.org/10.26508/lsa.202101068.

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Failure in the structural maintenance of the hair cell stereocilia bundle and ribbon synapse causes hearing loss. Here, we have studied how ER stress elicits hair cell pathology, using mouse models with inactivation of Manf (mesencephalic astrocyte-derived neurotrophic factor), encoding an ER-homeostasis-promoting protein. From hearing onset, Manf deficiency caused disarray of the outer hair cell stereocilia bundle and reduced cochlear sound amplification capability throughout the tonotopic axis. In high-frequency outer hair cells, the pathology ended in molecular changes in the stereocilia taper region and in strong stereocilia fusion. In high-frequency inner hair cells, Manf deficiency degraded ribbon synapses. The altered phenotype strongly depended on the mouse genetic background. Altogether, the failure in the ER homeostasis maintenance induced early-onset stereociliopathy and synaptopathy and accelerated the effect of genetic causes driving age-related hearing loss. Correspondingly, MANF mutation in a human patient induced severe sensorineural hearing loss from a young age onward. Thus, we present MANF as a novel protein and ER stress as a mechanism that regulate auditory hair cell maintenance in both mice and humans.

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40

Chole, Richard A., and Maggie Chiu. "Cochlear Hair Cell Stereocilia Loss in LP/J Mice with Bone Dysplasia of the Middle Ear." Annals of Otology, Rhinology & Laryngology 98, no. 6 (June 1989): 461–65. http://dx.doi.org/10.1177/000348948909800613.

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LP/J inbred mice spontaneously develop bony lesions of the middle ear and otic capsule that are similar to those of human otosclerosis and tympanosclerosis. These mice also have progressive loss of hearing due to cochlear hair cell loss. The purpose of this study was to describe quantitatively the deterioration and loss of cochlear hair cells to serve as a basis for future experiments attempting to alter the course of this disorder. Cochleas from 37 LP/J inbred mice were examined by scanning electron microscopy. The stereocilia loss in the cochlea was evident as early as 15 weeks of age and progressed from the basal turn to the apex. Outer hair cells were affected more than inner hair cells. As outer hair cells deteriorated we observed fusion, bending, and breakage of stereocilia. There were no apparent differences in the mode of deterioration among the three rows of outer hair cells. Stereocilia fusion of inner hair cells occurred at an older age, and giant, elongated stereocilia were found in some of the animals.

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Macic, Anes, Wei-Ching Lin, and Jong-Hoon Nam. "Two kinematic gains underlying the organ of Corti mechanotransduction." Journal of the Acoustical Society of America 151, no. 4 (April 2022): A258. http://dx.doi.org/10.1121/10.0011251.

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The organ of Corti (OoC) is the sensory epithelium in the mammalian hearing organ where vibrations are encoded into neural signals. The OoC vibrates due to external and internal agitations. Externally, differential fluid pressures across the OoC cause vibrations. Internally, actuator cells (outer hair cells) are known to boost the vibrations. These two agitations result in distinct vibration patterns. Eventually, these vibrations deflect the stereocilia bundle to activate mechanotransduction channels in them. How OoC vibrations result in the hair cell mechanotransduction is critical to hearing research, but a fundamental information (kinematic gain) has not been quantified clearly. Using the optical coherence tomography, we measured 2-D vibrations of the OoC in cochlear turns acutely excised from young Mongolian gerbils. The excised tissues were stimulated either mechanically or electrically, which are comparable to external or internal agitations, respectively. The stereocilia deflection was estimated from relative motion between overlying and underlying structures. Two kinematic gains were defined. Passive kinematic gain represents the amplitude ratio between the stereocilia deflection and the basilar membrane transverse vibration. Active kinematic gain represents the amplitude ratio between the stereocilia deflection and the outer hair cell length change. (Work supported by NIH NIDCD R01 DC014685.)

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Jia, S., S. Yang, W. Guo, and D. Z. Z. He. "Fate of Mammalian Cochlear Hair Cells and Stereocilia after Loss of the Stereocilia." Journal of Neuroscience 29, no. 48 (December 2, 2009): 15277–85. http://dx.doi.org/10.1523/jneurosci.3231-09.2009.

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Ciuman, R. R. "Auditory and vestibular hair cell stereocilia: relationship between functionality and inner ear disease." Journal of Laryngology & Otology 125, no. 10 (July 21, 2011): 991–1003. http://dx.doi.org/10.1017/s0022215111001459.

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AbstractThe stereocilia of the inner ear are unique cellular structures which correlate anatomically with distinct cochlear functions, including mechanoelectrical transduction, cochlear amplification, adaptation, frequency selectivity and tuning. Their function is impaired by inner ear stressors, by various types of hereditary deafness, syndromic hearing loss and inner ear disease (e.g. Ménière's disease). The anatomical and physiological characteristics of stereocilia are discussed in relation to inner ear malfunctions.

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Liu, Yan, Jieyu Qi, Xin Chen, Mingliang Tang, Cenfeng Chu, Weijie Zhu, Hui Li, et al. "Critical role of spectrin in hearing development and deafness." Science Advances 5, no. 4 (April 2019): eaav7803. http://dx.doi.org/10.1126/sciadv.aav7803.

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Inner ear hair cells (HCs) detect sound through the deflection of mechanosensory stereocilia. Stereocilia are inserted into the cuticular plate of HCs by parallel actin rootlets, where they convert sound-induced mechanical vibrations into electrical signals. The molecules that support these rootlets and enable them to withstand constant mechanical stresses underpin our ability to hear. However, the structures of these molecules have remained unknown. We hypothesized that αII- and βII-spectrin subunits fulfill this role, and investigated their structural organization in rodent HCs. Using super-resolution fluorescence imaging, we found that spectrin formed ring-like structures around the base of stereocilia rootlets. These spectrin rings were associated with the hearing ability of mice. Further, HC-specific, βII-spectrin knockout mice displayed profound deafness. Overall, our work has identified and characterized structures of spectrin that play a crucial role in mammalian hearing development.

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Karlsson, Kjell, and Åke Flock. "Graded mechanical properties of stereocilia." Hearing Research 22, no. 1-3 (January 1986): 92. http://dx.doi.org/10.1016/0378-5955(86)90084-5.

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Self, T., M. Mahony, J. Fleming, J. Walsh, S. D. Brown, and K. P. Steel. "Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells." Development 125, no. 4 (February 15, 1998): 557–66. http://dx.doi.org/10.1242/dev.125.4.557.

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The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

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Richardson, G. P., S. Bartolami, and I. J. Russell. "Identification of a 275-kD protein associated with the apical surfaces of sensory hair cells in the avian inner ear." Journal of Cell Biology 110, no. 4 (April 1, 1990): 1055–66. http://dx.doi.org/10.1083/jcb.110.4.1055.

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Immunological techniques have been used to generate both polyclonal and monoclonal antibodies specific for the apical ends of sensory hair cells in the avian inner ear. The hair cell antigen recognized by these antibodies is soluble in nonionic detergent, behaves on sucrose gradients primarily as a 16S particle, and, after immunoprecipitation, migrates as a polypeptide with a relative molecular mass of 275 kD on 5% SDS gels under reducing conditions. The antigen can be detected with scanning immunoelectron microscopy on the apical surface of the cell and on the stereocilia bundle but not on the kinocilium. Double label studies indicate that the entire stereocilia bundle is stained in the lagena macula (a vestibular organ), whereas in the basilar papilla (an auditory organ) only the proximal region of the stereocilia bundle nearest to the apical surface is stained. The monoclonal anti-hair cell antibodies do not stain brain, tongue, lung, liver, heart, crop, gizzard, small intestine, skeletal muscle, feather, skin, or eye tissues but do specifically stain renal corpuscles in the kidney. Experiments using organotypic cultures of the embryonic lagena macula indicate that the antibodies cause a significant increase in the steady-state stiffness of the stereocilia bundle but do not inhibit mechanotransduction. The antibodies should provide a suitable marker and/or tool for the purification of the apical sensory membrane of the hair cell.

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48

Caprara, Giusy A., Andrew A. Mecca, and Anthony W. Peng. "Decades-old model of slow adaptation in sensory hair cells is not supported in mammals." Science Advances 6, no. 33 (August 2020): eabb4922. http://dx.doi.org/10.1126/sciadv.abb4922.

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Hair cells detect sound and motion through a mechano-electric transduction (MET) process mediated by tip links connecting shorter stereocilia to adjacent taller stereocilia. Adaptation is a key feature of MET that regulates a cell’s dynamic range and frequency selectivity. A decades-old hypothesis proposes that slow adaptation requires myosin motors to modulate the tip-link position on taller stereocilia. This “motor model” depended on data suggesting that the receptor current decay had a time course similar to that of hair-bundle creep (a continued movement in the direction of a step-like force stimulus). Using cochlear and vestibular hair cells of mice, rats, and gerbils, we assessed how modulating adaptation affected hair-bundle creep. Our results are consistent with slow adaptation requiring myosin motors. However, the hair-bundle creep and slow adaptation were uncorrelated, challenging a critical piece of evidence upholding the motor model. Considering these data, we propose a revised model of hair cell adaptation.

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Tilney, M. S., L. G. Tilney, R. E. Stephens, C. Merte, D. Drenckhahn, D. A. Cotanche, and A. Bretscher. "Preliminary biochemical characterization of the stereocilia and cuticular plate of hair cells of the chick cochlea." Journal of Cell Biology 109, no. 4 (October 1, 1989): 1711–23. http://dx.doi.org/10.1083/jcb.109.4.1711.

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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.

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50

Höfer, Dirk, and Detlev Drenckhahn. "Cytoskeletal differences between stereocilia of the human sperm passageway and microvilli/stereocilia in other locations." Anatomical Record 245, no. 1 (May 1996): 57–64. http://dx.doi.org/10.1002/(sici)1097-0185(199605)245:1<57::aid-ar10>3.0.co;2-8.

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Journal articles on the topic 'Stereocilin'

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