Faculty Opinions recommendation of TMC1 forms the pore of mechanosensory transduction channels in vertebrate inner ear hair cells.

Sound-induced mechanical stimuli are detected by elaborate mechanosensory transduction (MT) machinery in highly specialized hair cells of the inner ear. Genetic studies of inherited deafness in the past decades have uncovered several molecular constituents of the MT complex, and intense debate has surrounded the molecular identity of the pore-forming subunits. How the MT components function in concert in response to physical stimulation is not fully understood. In this review, we summarize and discuss multiple lines of evidence supporting the hypothesis that transmembrane channel-like 1 is a long-sought MT channel subunit. We also review specific roles of other components of the MT complex, including protocadherin 15, cadherin 23, lipoma HMGIC fusion partner-like 5, transmembrane inner ear, calcium and integrin-binding family member 2, and ankyrins. Based on these recent advances, we propose a unifying theory of hair cell MT that may reconcile most of the functional discoveries obtained to date. Finally, we discuss key questions that need to be addressed for a comprehensive understanding of hair cell MT at molecular and atomic levels. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 6, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Faculty Opinions recommendation of TMC1 forms the pore of mechanosensory transduction channels in vertebrate inner ear hair cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733846310.793550292 ◽

2018 ◽

Author(s):

Donna Fekete

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Mechanosensory Transduction

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Faculty Opinions recommendation of Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13372023.14859074 ◽

2012 ◽

Cited By ~ 1

Author(s):

Jaime García-Añoveros

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Transmembrane Channel

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Faculty Opinions recommendation of TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718040306.793482643 ◽

2013 ◽

Author(s):

Andy Groves

Keyword(s):

Inner Ear ◽

Hair Cells

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Chimera states and frequency clustering in systems of coupled inner-ear hair cells

Chaos An Interdisciplinary Journal of Nonlinear Science ◽

10.1063/5.0056848 ◽

2021 ◽

Vol 31 (7) ◽

pp. 073142

Author(s):

Justin Faber ◽

Dolores Bozovic

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Chimera States

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Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

International Journal of Molecular Sciences ◽

10.3390/ijms22126497 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6497

Author(s):

Anna Ghilardi ◽

Alberto Diana ◽

Renato Bacchetta ◽

Nadia Santo ◽

Miriam Ascagni ◽

...

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Hair Cells ◽

Muscle Fibers ◽

Underlying Mechanism ◽

Loss Of Function ◽

Zebrafish Model ◽

Developmental Defects ◽

Inner Ear Development ◽

Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

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Identification and characterization of amphibian SLC26A5 using RNA-Seq

BMC Genomics ◽

10.1186/s12864-021-07798-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhongying Wang ◽

Qixuan Wang ◽

Hao Wu ◽

Zhiwu Huang

Keyword(s):

Amino Acid ◽

Inner Ear ◽

Hair Cells ◽

Rana Catesbeiana ◽

Site Directed Mutagenesis ◽

Amino Acid Residues ◽

Rna Seq ◽

American Bullfrog ◽

Frog Species

Abstract Background Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Limited knowledge of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage and the studies of it were quite rare with only one species identified. Results Here we report a new coding sequence of SLC26A5 for a frog species, Rana catesbeiana (the American bullfrog). In our study, the SLC26A5 gene of Rana has been mapped, sequenced and cloned successively using RNA-Seq. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of Rana’s inner ear and HEK293T cells transfected with this new coding gene. HEK293T cells expressing Rana prestin showed electrophysiological features similar to that of hair cells from its inner ear. Comparative studies of zebrafish, chick, Rana and an ancient frog species showed that chick and zebrafish prestin lacked NLC. Ancient frog’s prestin was functionally different from Rana. Conclusions We mapped and sequenced the SLC26A5 of the Rana catesbeiana from its inner ear cDNA using RNA-Seq. The Rana SLC26A5 cDNA was 2292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. This new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line. While comparing to its orthologs, the amphibian prestin has been evolutionarily changing its function and becomes more advanced than avian and teleost prestin.

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