Robert Fettiplace
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View article: Hair cell apoptosis and deafness in <i>Tmc1</i> mutations
Hair cell apoptosis and deafness in <i>Tmc1</i> mutations Open
Transmembrane channel-like protein 1 (TMC1), a pore-forming component of the mechano-electrical transducer (MET) channel in cochlear outer hair cells, is subject to numerous mutations causing deafness and hair cell death. We studied mice h…
View article: The mechanisms of frequency tuning in gecko auditory hair cells
The mechanisms of frequency tuning in gecko auditory hair cells Open
We developed an isolated auditory papilla of the crested gecko to record from the hair cells and explore the origins of frequency tuning. Low-frequency cells displayed electrical tuning, dependent on Ca2+-activated K+ channels; high-freque…
View article: Sensory transduction in auditory hair cells—PIEZOs can’t touch this
Sensory transduction in auditory hair cells—PIEZOs can’t touch this Open
In this Viewpoint, Holt, Fettiplace, and Müller weigh the evidence supporting a role for PIEZO and TMC channels in mechanosensory transduction in inner ear hair cells.
View article: LHFPL5 is a key element in force transmission from the tip link to the hair cell mechanotransducer channel
LHFPL5 is a key element in force transmission from the tip link to the hair cell mechanotransducer channel Open
During auditory transduction, sound-evoked vibrations of the hair cell stereociliary bundles open mechanotransducer (MET) ion channels via tip links extending from one stereocilium to its neighbor. How tension in the tip link is delivered …
View article: Cochlear tonotopy from proteins to perception
Cochlear tonotopy from proteins to perception Open
A ubiquitous feature of the auditory organ in amniotes is the longitudinal mapping of neuronal characteristic frequencies (CFs), which increase exponentially with distance along the organ. The exponential tonotopic map reflects variation i…
View article: The conductance and organization of the TMC1-containing mechanotransducer channel complex in auditory hair cells
The conductance and organization of the TMC1-containing mechanotransducer channel complex in auditory hair cells Open
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 characte…
View article: Atypical tuning and amplification mechanisms in gecko auditory hair cells
Atypical tuning and amplification mechanisms in gecko auditory hair cells Open
Significance Geckos are lizards capable of vocalization and can detect frequencies up to 5 kHz, but the mechanism of frequency discrimination is incompletely understood. The gecko’s auditory papilla has a unique arrangement over the high-f…
View article: The speed of the hair cell mechanotransducer channel revealed by fluctuation analysis
The speed of the hair cell mechanotransducer channel revealed by fluctuation analysis Open
Although mechanoelectrical transducer (MET) channels have been extensively studied, uncertainty persists about their molecular architecture and single-channel conductance. We made electrical measurements from mouse cochlear outer hair cell…
View article: New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells
New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells Open
Transmembrane channel-like protein isoform 1 (TMC1) is a major component of the mechano-electrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness. We report a new dominant human deafne…
View article: The contribution of TMC1 to adaptation of mechanoelectrical transduction channels in cochlear outer hair cells
The contribution of TMC1 to adaptation of mechanoelectrical transduction channels in cochlear outer hair cells Open
Key points Hair cell mechanoelectrical transducer channels are opened by deflections of the hair bundle about a resting position set by incompletely understood adaptation mechanisms. We used three characteristics to define adaptation in ha…
View article: A <i>Tmc1</i> mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells
A <i>Tmc1</i> mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells Open
Significance Cochlear hair cells transduce sound into electrical signals by activation of mechanically sensitive ion channels thought to be formed by TMC1. We generated a single aspartate/asparagine substitution in mouse TMC1 which is homo…
View article: Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea
Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea Open
Functional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs are required for normal stereociliary bundle development an…
View article: Spatiotemporal changes in the distribution of LHFPL5 in mice cochlear hair bundles during development and in the absence of PCDH15
Spatiotemporal changes in the distribution of LHFPL5 in mice cochlear hair bundles during development and in the absence of PCDH15 Open
Mechanosensory transduction by vertebrate hair cells depends on a protein complex at the tips of shorter stereocilia associated with mechanoelectrical transduction channels activated by tip links in the hair bundle. In mammalian hair cells…
View article: PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells
PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells Open
Throughout postnatal maturation of the mouse inner ear, cochlear hair cells display at least two types of mechanically gated ion channel: normal mechanotransducer (MT) channels at the tips of the stereocilia, activated by tension in interc…
View article: Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea
Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea Open
Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that …
View article: CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells Open
Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia,…
View article: Evaluation of Nestin Expression in the Developing and Adult Mouse Inner Ear
Evaluation of Nestin Expression in the Developing and Adult Mouse Inner Ear Open
Adult stem cells are undifferentiated cells with the capacity to proliferate and form mature tissue-specific cell types. Nestin is an intermediate filament protein used to identify cells with stem cell characteristics. Its expression has b…
View article: Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells
Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells Open
Significance Cochlear hair cells are the receptors of the inner ear, detecting sound stimuli by to-and-fro motion of their sensory hair bundle to open mechano-electrical transduction (MT) channels at the tips of the hairs. During embryonic…