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Neural Plasticity 2021Noise overexposure leads to hair cell loss, synaptic ribbon reduction, and auditory nerve deterioration, resulting in transient or permanent hearing loss depending on... (Review)
Review
Noise overexposure leads to hair cell loss, synaptic ribbon reduction, and auditory nerve deterioration, resulting in transient or permanent hearing loss depending on the exposure severity. Oxidative stress, inflammation, calcium overload, glutamate excitotoxicity, and energy metabolism disturbance are the main contributors to noise-induced hearing loss (NIHL) up to now. Gene variations are also identified as NIHL related. Glucocorticoid is the only approved medication for NIHL treatment. New pharmaceuticals targeting oxidative stress, inflammation, or noise-induced neuropathy are emerging, highlighted by the nanoparticle-based drug delivery system. Given the complexity of the pathogenesis behind NIHL, deeper and more comprehensive studies still need to be fulfilled.
Topics: Animals; Autophagy; Calcium; Clinical Trials, Phase II as Topic; DNA Repair; Drugs, Investigational; Energy Metabolism; Gap Junctions; Glutamic Acid; Hair Cells, Auditory; Hearing Loss, Noise-Induced; Humans; Inflammation; Isoindoles; Nanoparticles; Organoselenium Compounds; Oxidative Stress; Potassium Channels; Stereocilia
PubMed: 34306060
DOI: 10.1155/2021/4784385 -
Molecular and Cellular Neurosciences May 2022In the inner ear, the auditory and vestibular systems detect and translate sensory information regarding sound and balance. The sensory cells that transform mechanical... (Review)
Review
In the inner ear, the auditory and vestibular systems detect and translate sensory information regarding sound and balance. The sensory cells that transform mechanical input into an electrical signal in these systems are called hair cells. A specialized organelle on the apical surface of hair cells called the hair bundle detects mechanical signals. Displacement of the hair bundle causes mechanotransduction channels to open. The morphology and organization of the hair bundle, as well as the properties and characteristics of the mechanotransduction process, differ between the different hair cell types in the auditory and vestibular systems. These differences likely contribute to maximizing the transduction of specific signals in each system. This review will discuss the molecules essential for mechanotransduction and the properties of the mechanotransduction process, focusing our attention on recent data and differences between the auditory and vestibular systems.
Topics: Animals; Hair Cells, Auditory; Mammals; Mechanotransduction, Cellular
PubMed: 35218890
DOI: 10.1016/j.mcn.2022.103706 -
Current Opinion in Cell Biology Dec 2022Mechanosensory hair bundles are assembled from actin-based stereocilia that project from the apical surface of hair cells in the inner ear. Stereocilia architecture is... (Review)
Review
Mechanosensory hair bundles are assembled from actin-based stereocilia that project from the apical surface of hair cells in the inner ear. Stereocilia architecture is critical for the transduction of sound and accelerations, and structural defects in these mechano-sensors are a clinical cause of hearing and balance disorders in humans. Unconventional myosin motors are central to the assembly and shaping of stereocilia architecture. A sub-group of myosin motors with MyTH4-FERM domains (MYO7A, MYO15A) are particularly important in these processes, and hypothesized to act as transporters delivering structural and actin-regulatory cargos, in addition to generating force and tension. In this review, we summarize existing evidence for how MYO7A and MYO15A operate and how their dysfunction leads to stereocilia pathology. We further highlight emerging properties of the MyTH4/FERM myosin family and speculate how these new functions might contribute towards the acquisition and maintenance of mechano-sensitivity.
Topics: Humans; Actins; Myosins
PubMed: 36257241
DOI: 10.1016/j.ceb.2022.102132 -
Frontiers in Cell and Developmental... 2021
PubMed: 34869395
DOI: 10.3389/fcell.2021.800410 -
Journal of Zhejiang University....The incidence of blast injury has increased recently. As the ear is the organ most sensitive to blast overpressure, the most frequent injuries seen after blast exposure... (Review)
Review
The incidence of blast injury has increased recently. As the ear is the organ most sensitive to blast overpressure, the most frequent injuries seen after blast exposure are those affecting the ear. Blast overpressure affecting the ear results in sensorineural hearing loss, which is untreatable and often associated with a decline in the quality of life. Here, we review recent cases of blast-induced hearing dysfunction. The tympanic membrane is particularly sensitive to blast pressure waves, since such waves exert forces mainly at air-tissue interfaces within the body. However, treatment of tympanic membrane perforation caused by blast exposure is more difficult than that caused by other etiologies. Sensorineural hearing dysfunction after blast exposure is caused mainly by stereociliary bundle disruption on the outer hair cells. Also, a reduction in the numbers of synaptic ribbons in the inner hair cells and spiral ganglion cells is associated with hidden hearing loss, which is strongly associated with tinnitus or hyperacusis.
Topics: Blast Injuries; Ear; Hearing Loss, Conductive; Hearing Loss, Sensorineural; Humans; Tympanic Membrane Perforation
PubMed: 29770646
DOI: 10.1631/jzus.B1700051 -
Cellular Signalling Nov 2013Filopodia are sensors on both excitable and non-excitable cells. The sensing function is well documented in neurons and blood vessels of adult animals and is obvious... (Review)
Review
Filopodia are sensors on both excitable and non-excitable cells. The sensing function is well documented in neurons and blood vessels of adult animals and is obvious during dorsal closure in embryonic development. Nerve cells extend neurites in a bidirectional fashion with growth cones at the tips where filopodia are concentrated. Their sensing of environmental cues underpins the axon's ability to "guide," bypassing non-target cells and moving toward the target to be innervated. This review focuses on the role of filopodia structure and dynamics in the detection of environmental cues, including both the extracellular matrix (ECM) and the surfaces of neighboring cells. Other protrusions including the stereocilia of the inner ear and epididymus, the invertebrate Type I mechanosensors, and the elongated processes connecting osteocytes, share certain principles of organization with the filopodia. Actin bundles, which may be inside or outside of the excitable cell, function to transduce stress from physical perturbations into ion signals. There are different ways of detecting such perturbations. Osteocyte processes contain an actin core and are physically anchored on an extracellular structure by integrins. Some Type I mechanosensors have bridge proteins that anchor microtubules to the membrane, but bundles of actin in accessory cells exert stress on this complex. Hair cells of the inner ear rely on attachments between the actin-based protrusions to activate ion channels, which then transduce signals to afferent neurons. In adherent filopodia, the focal contacts (FCs) integrated with ECM proteins through integrins may regulate integrin-coupled ion channels to achieve signal transduction. Issues that are not understood include the role of Ca(2+) influx in filopodia dynamics and how integrins coordinate or gate signals arising from perturbation of channels by environmental cues.
Topics: Actins; Animals; Calcium; Chemotaxis; Ear, Inner; Epididymis; Extracellular Matrix; Humans; Integrins; Male; Mechanoreceptors; Neurons; Osteocytes; Pseudopodia; Signal Transduction; Stereocilia
PubMed: 23876793
DOI: 10.1016/j.cellsig.2013.07.006 -
Current Biology : CB May 2021Filopodia, microvilli and stereocilia represent an important group of plasma membrane protrusions. These specialized projections are supported by parallel bundles of... (Review)
Review
Filopodia, microvilli and stereocilia represent an important group of plasma membrane protrusions. These specialized projections are supported by parallel bundles of actin filaments and have critical roles in sensing the external environment, increasing cell surface area, and acting as mechanosensors. While actin-associated proteins are essential for actin-filament elongation and bundling in these protrusions, myosin motors have a surprising role in the formation and extension of filopodia and stereocilia and in the organization of microvilli. Actin regulators and specific myosins collaborate in controlling the length of these structures. Myosins can transport cargoes along the length of these protrusions, and, in the case of stereocilia and microvilli, interactions with adaptors and cargoes can also serve to anchor adhesion receptors to the actin-rich core via functionally conserved motor-adaptor complexes. This review highlights recent progress in understanding the diverse roles myosins play in filopodia, microvilli and stereocilia.
Topics: Actins; Microvilli; Myosins; Pseudopodia; Stereocilia
PubMed: 34033792
DOI: 10.1016/j.cub.2021.04.005 -
Hearing Research Sep 2023Inner ear hair cells assemble mechanosensitive hair bundles on their apical surface that transduce sounds and accelerations. Each hair bundle is comprised of ∼ 100... (Review)
Review
Inner ear hair cells assemble mechanosensitive hair bundles on their apical surface that transduce sounds and accelerations. Each hair bundle is comprised of ∼ 100 individual stereocilia that are arranged into rows of increasing height and width; their specific and precise architecture being necessary for mechanoelectrical transduction (MET). The actin cytoskeleton is fundamental to establishing this architecture, not only by forming the structural scaffold shaping each stereocilium, but also by composing rootlets and the cuticular plate that together provide a stable foundation supporting each stereocilium. In concert with the actin cytoskeleton, a large assortment of actin-binding proteins (ABPs) function to cross-link actin filaments into specific topologies, as well as control actin filament growth, severing, and capping. These processes are individually critical for sensory transduction and are all disrupted in hereditary forms of human hearing loss. In this review, we provide an overview of actin-based structures in the hair bundle and the molecules contributing to their assembly and functional properties. We also highlight recent advances in mechanisms driving stereocilia elongation and how these processes are tuned by MET.
Topics: Humans; Hair Cells, Auditory; Actin Cytoskeleton; Deafness; Hair Cells, Auditory, Inner; Actins; Stereocilia
PubMed: 37300948
DOI: 10.1016/j.heares.2023.108817 -
The Journal of Neuroscience : the... May 2023The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding...
The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs of / double knock-out mice of either sex. Furthermore, we show that and transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs. transcripts are highly expressed in the striolar region, and knock-out of affects stereocilia maintenance in striolar VHCs. In contrast, transcripts are highly expressed in the extrastriolar region, and knock-out of mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out of and affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs. Calcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected in knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, and / double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way. and transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected in or knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.
Topics: Animals; Mice; Calcium; Hair Cells, Vestibular; Integrins; Mice, Knockout; Stereocilia
PubMed: 37001993
DOI: 10.1523/JNEUROSCI.1807-22.2023 -
Proceedings of the National Academy of... Oct 2022Transmembrane channel-like protein 1 (TMC1) is thought to form the ion-conducting pore of the mechanoelectrical transducer (MET) channel in auditory hair cells. Using...
Transmembrane channel-like protein 1 (TMC1) is thought to form the ion-conducting pore of the mechanoelectrical transducer (MET) channel in auditory hair cells. Using single-channel analysis and ionic permeability measurements, we characterized six missense mutations in the purported pore region of mouse TMC1. All mutations reduced the Ca permeability of the MET channel, triggering hair cell apoptosis and deafness. In addition, p.E520Q and p.D528N reduced channel conductance, whereas p.W554L and p.D569N lowered channel expression without affecting the conductance. p.M412K and p.T416K reduced only the Ca permeability. The consequences of these mutations endorse TMC1 as the pore of the MET channel. The accessory subunits, LHFPL5 and TMIE, are thought to be involved in targeting TMC1 to the tips of the stereocilia. We found sufficient expression of TMC1 in outer hair cells of and knockout mice to determine the properties of the channels, which could still be gated by hair bundle displacement. Single-channel conductance was unaffected in but was reduced in , implying TMIE very likely contributes to the pore. Both the working range and half-saturation point of the residual MET current in were substantially increased, suggesting that LHFPL5 is part of the mechanical coupling between the tip-link and the MET channel. Based on counts of numbers of stereocilia per bundle, we estimate that each PCDH15 and LHFPL5 monomer may contact two channels irrespective of location.
Topics: Animals; Hair Cells, Auditory, Outer; Hair Cells, Vestibular; Mechanotransduction, Cellular; Membrane Proteins; Mice; Mice, Knockout; Stereocilia
PubMed: 36191207
DOI: 10.1073/pnas.2210849119