Review
Biochemistry & Molecular Biology
Shuang Liu, Shufeng Wang, Linzhi Zou, Wei Xiong
Summary: This review summarizes the progress on the molecular and cellular mechanisms of the mechano-electrical transduction (MET) channel in cochlear hair cells and recent studies on TMC1, the molecule likely to form the MET channel pore.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Alexandra L. Scharr, Daibhid O. Maoileidigh, Anthony J. Ricci
Summary: The hair bundle, composed of mechanically coupled stereocilia, is a universal mechanosensory organelle in auditory, vestibular, and lateral-line systems. The dynamics of individual stereocilia in response to bundle stimulus has not been quantified. By stimulating and tracking individual inner-hair-cell stereocilia, it was found that nonuniform stimulation led to dissimilar stereociliary displacements and stereocilia closer to the stimulator moved more. The weak coupling between stereocilia suggests that more uniform stimulation across the tallest stereocilia is required to enhance the receptor current.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Marco Derudas, Molly O'Reilly, Nerissa K. Kirkwood, Emma J. Kenyon, Sybil Grimsey, Sian R. Kitcher, Shawna Workman, James C. Bull, Simon E. Ward, Corne J. Kros, Guy P. Richardson
Summary: The styryl dye FM1-43 is commonly used to study endocytosis, but it also acts as a permeant blocker of the MET channel in sensory hair cells. Structural modifications of FM1-43 affect its ability to block the MET channel, as well as its loading into hair cells. Some derivatives of FM1-43 demonstrate otoprotective potential in cochlear cultures.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Katharine K. Miller, Patrick Atkinson, Kyssia Ruth Mendoza, Daibhid Maoileidigh, Nicolas Grillet
Summary: The hair bundle of hair cells is a mechanosensory organelle that detects mechanical stimuli, and its dimensions and characteristics affect how it responds to stimuli. Measurements on mouse inner hair cells concluded that different fixation methods can influence the size and mechanical properties of hair bundles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Bingxue Li, Songling Li, Honglan Zheng, Zhiqiang Yan
Summary: Research shows that in Drosophila larvae, the MET currents in Cho neurons are mediated by two TRPV channels, NAN and IAV, with the C-terminal residues 857 through 990 of IAV regulating the kinetics of MET currents. Additionally, the NompC channel contributes to the adaptation of auditory transduction currents.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Xufeng Qiu, Ulrich Muller
Summary: Organisms of all phyla possess mechanosensitive ion channels that serve a wide range of physiological functions. The mechanotransduction machinery of cochlear hair cells is a complex and crucial force-sensing machine. Recent discoveries have shed light on its composition and its impact on the development and function of the auditory system.
Review
Cell Biology
Mohammad Farhadi, Ehsan Razmara, Maryam Balali, Yeganeh Hajabbas Farshchi, Masoumeh Falah
Summary: Disruptions in cellular mechanisms can lead to hearing impairment, with TMIE protein playing a critical role in maintaining sensory hair cells and being associated with hereditary deafness.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Nurunisa Akyuz, K. Domenica Karavitaki, Bifeng Pan, Panos Tamvakologos, Kelly P. Brock, Yaqiao Li, Debora S. Marks, David P. Corey
Summary: This study investigated the effects of 12 mutations on the mechanical gating of transduction currents in native hair cells of Tmc1/2-null mice expressing virally introduced TMC1 variants. The results showed that mutations within the pore-lining TM4 and TM6 helices modified gating, reducing force sensitivity or changing the open probability of the channels.
Article
Multidisciplinary Sciences
Jie Li, Shuang Liu, Chenmeng Song, Qun Hu, Zhikai Zhao, Tuantuan Deng, Yi Wang, Tong Zhu, Linzhi Zou, Shufeng Wang, Jiaofeng Chen, Lian Liu, Hanqing Hou, Kexin Yuan, Hairong Zheng, Zhiyong Liu, Xiaowei Chen, Wenzhi Sun, Bailong Xiao, Wei Xiong
Summary: The knockout of the mechanosensitive ion channel PIEZO2 in cochlea disrupts ultrasonic hearing in mice, but not low-frequency hearing. Deletion of Piezo2 in outer hair cells specifically abolishes associative learning in mice during hearing exposure at ultrasonic frequencies. The study demonstrates that OHCs serve as effector cells, combining with PIEZO2 as an essential molecule for ultrasonic hearing in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Shaoyuan Zhu, Zongwei Chen, Haoming Wang, Brian M. McDermott
Summary: Hair cells in the ear show dependency on Tmc proteins based on organ, subtype, position, and axis of best sensitivity, suggesting heterogeneity in mechanotransduction mechanisms within sensory systems.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yuqi Qin, Daqi Yu, Dan Wu, Jiangqing Dong, William Thomas Li, Chang Ye, Kai Chit Cheung, Yingyi Zhang, Yun Xu, YongQiang Wang, Yun Stone Shi, Shangyu Dang
Summary: This study determines the cryo-EM structure of mouse TMEM63C and reveals its structural differences compared to other TMEM63 proteins. The coupling of TM0 and TM6 is shown to play important roles in channel activity. Additionally, it is discovered that TMEM63C exists primarily as a monomer, while TMEM63B can exist as a mixture of monomer and dimer, suggesting oligomerization as a regulatory mechanism.
NATURE COMMUNICATIONS
(2023)
Review
Neurosciences
Basile Tarchini
Summary: Sensory hair cells detect mechanical stimuli through their hair bundle structure, which determines their directional sensitivity. Coordinated orientation of same-side hair cells ensures the delivery of local group response, while the differential orientation of opposite-side hair cells provides bidirectional sensitivity at the organ level.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biophysics
Wang Zheng, Jeffrey R. Holt
Summary: This review summarizes the research progress on hair cell mechanosensory transduction, proposing the hypothesis of the MT channel subunit and discussing the specific roles of other components of the MT complex. A unifying theory is proposed to reconcile most functional discoveries, and key questions for a comprehensive understanding of hair cell MT at molecular and atomic levels are also discussed.
ANNUAL REVIEW OF BIOPHYSICS, VOL 50, 2021
(2021)
Article
Biology
Ge Gao, Shuyu Guo, Quan Zhang, Hefei Zhang, Cuizhen Zhang, Gang Peng
Summary: Unbiased genetic screens have identified several uncharacterized genes involved in hearing loss, indicating that certain biological processes crucial for auditory function have not yet been explored. In this study, disruption of the gene Kiaa1024L/Minar2 was found to cause hearing loss in zebrafish. The mutant showed defects in mechanotransduction, hair bundle structure, and cholesterol localization, suggesting that Kiaa1024L/Minar2 plays a critical role in regulating cholesterol distribution and ensuring normal hearing.
Article
Neurosciences
Maryline Beurg, Lisa A. Schimmenti, Alaa Koleilat, Sami S. Amr, Andrea Oza, Amanda J. Barlow, Angela Ballesteros, Robert Fettiplace
Summary: TMC1 is a crucial protein in causing deafness, with mutations like T422K affecting Ca2+ permeability and resting open probability of the MET channel. Adjacent mutations to TMC1, such as L416R, G417R, and M418K, show similar channel effects in mice, suggesting a common mechanism for deafness. Comparisons between dominant and recessive mutations near the channel pore reveal differences in channel conductance and transduction loss.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Mary E. O'Sullivan, Yohan Song, Robert Greenhouse, Randy Lin, Adela Perez, Patrick J. Atkinson, Jacob P. MacDonald, Zehra Siddiqui, Dennis Lagasca, Kate Comstock, Markus E. Huth, Alan G. Cheng, Anthony J. Ricci
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Neurosciences
Alix Trouillet, Katharine K. Miller, Shefin Sam George, Pei Wang, Noor-E-Seher Ali, Anthony Ricci, Nicolas Grillet
Summary: The study identified the importance of the Loxhd1/DFNB77 gene in the mechanotransduction process in cochlear hair cells. Mutations in Loxhd1 in mice resulted in mechanotransduction defects without morphological defects or reduction in tip link number. These findings revealed a novel LOXHD1-dependent step in hair bundle development critical for mechanotransduction in mature hair cells and normal hearing function in mice and humans.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Mamiko Niwa, Eric D. Young, Elisabeth Glowatzki, Anthony J. Ricci
Summary: The study revealed that pillar synapses mature later than modiolar synapses in the hair cell-spiral ganglion neuron synapse, with a significant difference in release process which may partly drive afferent firing properties.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Cell Biology
Anthony W. Peng, Alexandra L. Scharr, Giusy A. Caprara, Dailey Nettles, Charles R. Steele, Anthony J. Ricci
Summary: The sensitivity of hair cells to mechanical stimuli is found in the sensory hair bundle, which is composed of actin-filled stereocilia arranged in a staircase pattern. Stimulation of the hair bundle results in non-uniform expansion, primarily due to fluid dynamics with a minor contribution from hair bundle architecture. Additionally, in response to stimulation, the hair bundle exhibits rapid and slow motions, described by a double viscoelastic process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Yanli Wang, Charles R. Steele, Sunil Puria, Anthony J. Ricci
Summary: In vertebrate hearing organs, mechanical vibrations are converted to ionic currents through mechanoelectrical-transduction (MET) channels. High-speed imaging in an ex vivo organ of Corti (OoC) mouse preparation revealed how the OoC and hair bundle rotate, and how individual stereocilia move semi-independently within a given hair bundle. This study sheds light on the in situ intra-hair-bundle motions of stereocilia, providing insight into the unique tuning mechanisms of mammalian cochleae.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfred L. Nuttall, Sherri M. Jones, Dongseok Choi, Thomas B. Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie
Summary: The stereocilia rootlet plays a critical role in protecting vertebrate hair cells from overstimulation. This study demonstrates that the ANKRD24 protein concentrates at the insertion point of the stereocilia, forming a ring and binding with TRIOBP-5 to maintain its distribution. ANKRD24 and TRIOBP-5 together organize the rootlets, enabling long-term auditory resilience.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jinkyung Kim, Anthony J. Ricci
Summary: This study tracks the entry and targeting process of a commonly used antibiotic, aminoglycosides (AGs), in the cochlea. The authors found that AGs enter the cochlea through the stria vascularis and selectively target cochlear sensory hair cells (HCs). They also identified the mechanotransducer channel and megalin as key factors in AG uptake. Blocking megalin prevented AG accumulation in HCs and reduced HC degeneration and hearing loss.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Jinkyung Kim, Sriram Hemachandran, Alan G. Cheng, Anthony J. Ricci
Summary: Aminoglycosides are potent antibiotics commonly prescribed worldwide, but their use carries the risk of ototoxicity and there are currently no approved antidotes. Therefore, it is important to review recent advances in understanding aminoglycoside ototoxicity and potential intervention sites for preventing ototoxicity.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Jinkyung Kim, Anthony J. Ricci
Summary: This article introduces a surgical procedure that allows effective imaging of cochlear cells in hearing mice, while preserving hearing thresholds. This technique may enable real-time tracking of ototoxic drug transport into the cochleae and monitoring of sound-evoked functional activity in multiple cochlear cells. It may also have implications for improving cochlear implantation in humans.
Article
Cell Biology
Paroma Chatterjee, Clive P. Morgan, Jocelyn F. Krey, Connor Benson, Jennifer Goldsmith, Michael Bateschell, Anthony J. Ricci, Peter G. Barr-Gillespie
Summary: GIPC3 is initially localized to the cytoplasm of hair cells in the cochlea and then concentrated at cell junctions during postnatal development. Gipc3K & DEG;/K & DEG; mice have normal mechanotransduction currents but lack auditory brainstem response. The disruption of cell junctions and altered distribution of GIPC3 suggest that GIPC3 and MYO6 play a role in shaping the cuticular plate.
JOURNAL OF CELL SCIENCE
(2023)
Article
Neurosciences
Alexandra L. Scharr, Daibhid O. Maoileidigh, Anthony J. Ricci
Summary: The hair bundle, composed of mechanically coupled stereocilia, is a universal mechanosensory organelle in auditory, vestibular, and lateral-line systems. The dynamics of individual stereocilia in response to bundle stimulus has not been quantified. By stimulating and tracking individual inner-hair-cell stereocilia, it was found that nonuniform stimulation led to dissimilar stereociliary displacements and stereocilia closer to the stimulator moved more. The weak coupling between stereocilia suggests that more uniform stimulation across the tallest stereocilia is required to enhance the receptor current.
JOURNAL OF NEUROSCIENCE
(2023)
Meeting Abstract
Biophysics
Shefin Sam George, Thomas Effertz, Anthony J. Ricci
BIOPHYSICAL JOURNAL
(2023)
Meeting Abstract
Biophysics
Shefin Sam George, Amel El Bahloul-Jaziri, Anthony J. Ricci
BIOPHYSICAL JOURNAL
(2023)
Meeting Abstract
Biophysics
Zenghao Zhu, Anthony J. Ricci, Daibhid O. Maoileidigh
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemical Research Methods
Shefin S. George, Charles R. Steele, Anthony J. Ricci
Summary: This method outlines the procedure for performing two-photon FRAP on the stereocilia of live cochlear inner hair cells to assess membrane diffusivity, and also provides details on microscope setup, calibration, parameter setting, and data analysis. For more information, refer to the publication by George et al. (2020).
