scholarly journals LMO7 deficiency reveals the significance of the cuticular plate for hearing function

2018 ◽  
Author(s):  
Ting-Ting Du ◽  
James B. Dewey ◽  
Elizabeth L. Wagner ◽  
Shimon P. Francis ◽  
Edward Perez-Reyes ◽  
...  
Keyword(s):  
Hair Cell ◽  
Late Onset ◽  
Hair Bundle ◽  
Cell Protein ◽  
Inner Hair Cell ◽  
Filamentous Actin ◽  
Cuticular Plate ◽  
Hearing Function ◽  
Cochlear Tuning ◽  
And Function

AbstractSensory hair cells, the mechanoreceptors of the auditory and vestibular system, harbor two specialized organelles, the hair bundle and the cuticular plate. Both subcellular structures have adapted to facilitate the remarkable sensitivity and speed of hair cell mechanotransduction. While the mechanosensory hair bundle is extensively studied, the molecules and mechanisms mediating the development and function of the cuticular plate are poorly understood. The cuticular plate is believed to provide a rigid foundation for stereociliar pivot movements, but specifics about its function, especially the significance of its integrity for long-term maintenance of hair cell mechanotransduction, are not known. In this study, we describe the discovery of a hair cell protein called LIM only protein 7 (LMO7). In the hair cell, LMO7 is specifically localized in the cuticular plate. Lmo7 KO mice suffer multiple deficiencies in the cuticular plate, including reduced filamentous actin density and abnormal length and distribution of stereociliar rootlets. In addition to the cuticular plate defects, older Lmo7 KO mice develop abnormalities in inner hair cell stereocilia. Together, these defects affect cochlear tuning and sensitivity and give rise to late-onset progressive hearing loss.

scholarly journals Actin Crosslinking Family Protein 7 Deficiency Does Not Impair Hearing in Young Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Benjamin L. Gilbert ◽  
Shaoyuan Zhu ◽  
Ahlam Salameh ◽  
Shenyu Sun ◽  
Kumar N. Alagramam ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Conditional Knockout ◽  
Cell Protein ◽  
Apical Region ◽  
Filamentous Actin ◽  
Cuticular Plate ◽  
Family Protein ◽  
Young Mice

To enable hearing, the sensory hair cell contains specialized subcellular structures at its apical region, including the actin-rich cuticular plate and circumferential band. ACF7 (actin crosslinking family protein 7), encoded by the gene Macf1 (microtubule and actin crosslinking factor 1), is a large cytoskeletal crosslinking protein that interacts with microtubules and filamentous actin to shape cells. ACF7 localizes to the cuticular plate and the circumferential band in the hair cells of vertebrates. The compelling expression pattern of ACF7 in hair cells, combined with conserved roles of this protein in the cytoskeleton of various cell types in invertebrates and vertebrates, led to the hypothesis that ACF7 performs a key function in the subcellular architecture of hair cells. To test the hypothesis, we conditionally target Macf1 in the inner ears of mice. Surprisingly, our data show that in young, but mature, conditional knockout mice cochlear hair cell survival, planar cell polarity, organization of the hair cells within the organ of Corti, and capacity to hear are not significantly impacted. Overall, these results fail to support the hypothesis that ACF7 is an essential hair cell protein in young mice, and the purpose of ACF7 expression in the hair cell remains to be understood.

scholarly journals Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses

2009 ◽  
Vol 18 (23) ◽  
pp. 4615-4628 ◽  
Author(s):  
Isabelle Roux ◽  
Suzanne Hosie ◽  
Stuart L. Johnson ◽  
Amel Bahloul ◽  
Nadège Cayet ◽  
...  
Keyword(s):  
Hair Cell ◽  
Myosin Vi ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
And Function

Nanofluidics of Mammalian Hearing

2011 ◽  
Author(s):  
Sonya T. Smith ◽  
Richard Chadwick
Keyword(s):  
Ion Channels ◽  
Hair Cell ◽  
Flow Patterns ◽  
Hair Bundle ◽  
Tectorial Membrane ◽  
Inner Hair Cell ◽  
Fluid Shear ◽  
Acoustic Stimuli ◽  
Molecular Gates

The inner hair cell stereocilia bundle performs the role of transducer in mammalian hearing. Acoustic stimuli deflect the hair bundle to open ion channels, resulting in cation influx and the subsequent release of a neurotransmitter at the base of the cell. Hypotheses for this transduction include fluid shear-driven motion between the tectorial membrane and the reticular lamina to deflect the bundle. It is presumed that ‘molecular gates’ sense tension in tip-links that connect adjacent stepped rows of stereocilia to open the channels. However, almost nothing is known about the endolymphatic flow in the micron-sized gap surrounding the bundle and the nanoscale sized gaps between individual stereocilia rows and between individual bundles. Here we show with nanometer resolution, how each row of stereocilia, their associated tip links and gates and the corresponding flow patterns move in response to acoustical input.

scholarly journals In situ motions of individual inner-hair-cell stereocilia from stapes stimulation in adult mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yanli Wang ◽  
Charles R. Steele ◽  
Sunil Puria ◽  
Anthony J. Ricci
Keyword(s):  
Hair Cell ◽  
High Speed ◽  
Ex Vivo ◽  
Ionic Currents ◽  
Hair Bundle ◽  
Sensory Cells ◽  
Apical Surface ◽  
Inner Hair Cell ◽  
High Speed Imaging

AbstractIn vertebrate hearing organs, mechanical vibrations are converted to ionic currents through mechanoelectrical-transduction (MET) channels. Concerted stereocilia motion produces an ensemble MET current driving the hair-cell receptor potential. Mammalian cochleae are unique in that the tuning of sensory cells is determined by their mechanical environment and the mode of hair-bundle stimulation that their environment creates. However, little is known about the in situ intra-hair-bundle motions of stereocilia relative to one another, or to their environment. In this study, high-speed imaging allowed the stereocilium and cell-body motions of inner hair cells to be monitored in an ex vivo organ of Corti (OoC) mouse preparation. We have found that the OoC rotates about the base of the inner pillar cell, the hair bundle rotates about its base and lags behind the motion of the apical surface of the cell, and the individual stereocilia move semi-independently within a given hair bundle.

scholarly journals Essential Role of Sptan1 in Cochlear Hair Cell Morphology and Function Via Focal Adhesion Signaling

2021 ◽  
Author(s):  
Qingxiu Yao ◽  
Hui Wang ◽  
Hengchao Chen ◽  
Zhuangzhuang Li ◽  
Yumeng Jiang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Focal Adhesion ◽  
Hair Cells ◽  
Focal Adhesions ◽  
Organ Of Corti ◽  
Cochlear Hair Cell ◽  
Cuticular Plate ◽  
And Function

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.

The Diversified Form and Function of Cochlear Afferents

2018 ◽  
pp. 36-58 ◽  
Author(s):  
Paul Albert Fuchs
Keyword(s):  
Hair Cell ◽  
Outer Hair Cell ◽  
Large Diameter ◽  
Great Majority ◽  
Outer Hair Cells ◽  
Type I ◽  
Type Ii ◽  
Inner Hair Cell ◽  
Form And Function ◽  
And Function

Cochlear afferents differ in form and function. The great majority are type I, large diameter, myelinated neurons that contact a single inner hair cell to transmit acoustic information. Each inner hair cell is presynaptic to a pool of 10–30 type I afferents, among which spontaneous activity and acoustic threshold vary widely. Variation in the number, voltage-gating, and density of L-type calcium channels at each presynaptic active zone (ribbon) may dictate this functional diversity. Despite contacting large numbers of outer hair cells, the scarce, unmyelinated type II afferents are acoustically insensitive, and only weakly depolarized by outer hair cell transmitter release. However, type II afferents respond strongly to adenosine triphosphate released by cochlear tissue damage, providing a biological basis for painful hearing (noxacusis).

scholarly journals Relating structure and function of inner hair cell ribbon synapses

2015 ◽  
Vol 361 (1) ◽  
pp. 95-114 ◽  
Author(s):  
C. Wichmann ◽  
T. Moser
Keyword(s):  
Hair Cell ◽  
Structure And Function ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
And Function

Inner Hair Cell of the Organ of the Corti

2020 ◽  
Author(s):  
Keyword(s):  
Hair Cell ◽  
Inner Hair Cell

scholarly journals Common and rare genetic variants that could contribute to severe otitis media in an Australian Aboriginal population

2021 ◽  
Author(s):  
Sarra E Jamieson ◽  
Michaela Fakiola ◽  
Dave Tang ◽  
Elizabeth Scaman ◽  
Genevieve Syn ◽  
...  
Keyword(s):  
Hair Cell ◽  
Otitis Media ◽  
Genetic Risk ◽  
Transforming Growth Factor ◽  
Rare Variants ◽  
Protein Coding ◽  
Gene Sets ◽  
Growth Factor Signalling ◽  
Rare Genetic Variants ◽  
And Function

Abstract Background Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians. Methods Illumina ® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all≥0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥ 15) were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥ 3 consecutive years). Rare (ExAC_all≤0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM. Results FUMA analysis identified two plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G=3.62x10 -6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G=3.67x10 -6) encoding neuronal regeneration related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for “abnormal ear” (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signalling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly. Conclusions This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.

Sign in / Sign up

Export Citation Format

Share Document