The micromachinery of mechanotransduction in hair cells.

Mechanical stimuli generated by head movements and changes in sound pressure are detected by hair cells with amazing speed and sensitivity. The mechanosensitive organelle, the hair bundle, is a highly elaborated structure of actin-based stereocilia arranged in precise rows of increasing height. Extracellular linkages contribute to its cohesion and convey forces to mechanically gated channels. Channel opening is nearly instantaneous and is followed by a process of sensory adaptation that keeps the channels poised in their most sensitive range. This process is served by motors, scaffolds, and homeostatic mechanisms. The molecular constituents of this process are rapidly being elucidated, especially by the discovery of deafness genes and antibody targets.

[1]  R. Goodyear,et al.  The Tip-Link Antigen, a Protein Associated with the Transduction Complex of Sensory Hair Cells, Is Protocadherin-15 , 2006, The Journal of Neuroscience.

[2]  J. T. Corwin,et al.  Lighting up the Senses: FM1-43 Loading of Sensory Cells through Nonselective Ion Channels , 2003, The Journal of Neuroscience.

[3]  Pierre Legrain,et al.  Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle , 2002, The EMBO journal.

[4]  T. Vogt,et al.  Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Eatock,et al.  Adaptation in hair cells. , 2000, Annual review of neuroscience.

[6]  A J Ricci,et al.  The Endogenous Calcium Buffer and the Time Course of Transducer Adaptation in Auditory Hair Cells , 1998, The Journal of Neuroscience.

[7]  Peter G. Gillespie,et al.  Plasma Membrane Ca2+-ATPase Isoform 2a Is the PMCA of Hair Bundles , 2001, The Journal of Neuroscience.

[8]  Atsuko Mizuno,et al.  Hearing impairment in TRPV4 knockout mice , 2005, Neuroscience Letters.

[9]  J. R. Holt,et al.  Developmental acquisition of sensory transduction in hair cells of the mouse inner ear , 2003, Nature Neuroscience.

[10]  A J Ricci,et al.  Active Hair Bundle Motion Linked to Fast Transducer Adaptation in Auditory Hair Cells , 2000, The Journal of Neuroscience.

[11]  Christine Petit,et al.  Cadherin 23 is a component of the transient lateral links in the developing hair bundles of cochlear sensory cells. , 2005, Developmental biology.

[12]  S. Riazuddin,et al.  Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. , 2001, American journal of human genetics.

[13]  U. Wolfrum,et al.  Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease. , 2006, Experimental eye research.

[14]  M G Evans,et al.  Activation and adaptation of transducer currents in turtle hair cells. , 1989, The Journal of physiology.

[15]  D. Corey,et al.  Ca2+ changes the force sensitivity of the hair-cell transduction channel. , 2006, Biophysical journal.

[16]  David Julius,et al.  TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents , 2006, Cell.

[17]  C. G. Wright,et al.  Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development , 2006, Journal of the Association for Research in Otolaryngology.

[18]  H. Ohmori,et al.  Mechano‐electrical transduction currents in isolated vestibular hair cells of the chick. , 1985, The Journal of physiology.

[19]  C. G. Wright,et al.  Neuroepithelial defects of the inner ear in a new allele of the mouse mutation Ames waltzer , 2000, Hearing Research.

[20]  M. Poot,et al.  Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase that can regulate cell survival and proliferation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Gillespie,et al.  Myosin-1c Interacts with Hair-Cell Receptors through Its Calmodulin-Binding IQ Domains , 2002, The Journal of Neuroscience.

[22]  R. Fettiplace,et al.  Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph , 1998, The Journal of physiology.

[23]  M. Paparella,et al.  Structure of the stereocilia side links and morphology of auditory hair bundle in relation to noise exposure in the chinchilla , 2003, Journal of neurocytology.

[24]  A. Hudspeth,et al.  Identification of a 120 kd hair-bundle myosin located near stereociliary tips , 1993, Neuron.

[25]  Peter Michaely,et al.  Nanospring behaviour of ankyrin repeats , 2006, Nature.

[26]  R. Fettiplace,et al.  The Distribution of Calcium Buffering Proteins in the Turtle Cochlea , 2003, The Journal of Neuroscience.

[27]  R. Goodyear,et al.  The structure of tip links and kinocilial links in avian sensory hair bundles. , 2004, Biophysical journal.

[28]  Robert Fettiplace,et al.  The Transduction Channel Filter in Auditory Hair Cells , 2005, The Journal of Neuroscience.

[29]  J. R. Holt,et al.  Fast Adaptation in Vestibular Hair Cells Requires Myosin-1c Activity , 2005, Neuron.

[30]  Leong L Ng,et al.  Identification of mRNA transcripts and immunohistochemical localization of Na/H exchanger isoforms in gerbil inner ear , 1998, Hearing Research.

[31]  G. Richardson,et al.  Hair Cells Require Phosphatidylinositol 4,5-Bisphosphate for Mechanical Transduction and Adaptation , 2004, Neuron.

[32]  A J Hudspeth,et al.  The selectivity of the hair cell's mechanoelectrical-transduction channel promotes Ca2+ flux at low Ca2+ concentrations. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  K. Steel,et al.  Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. , 1998, Development.

[34]  E. Ostap,et al.  Dynamics of Myo1c (Myosin-Iβ) Lipid Binding and Dissociation* , 2002, The Journal of Biological Chemistry.

[35]  Peter G. Gillespie,et al.  Cadherin 23 is a component of the tip link in hair-cell stereocilia , 2004, Nature.

[36]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[37]  Bechara Kachar,et al.  Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice , 2005, Hearing Research.

[38]  Aziz El-Amraoui,et al.  Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. , 2005, Human molecular genetics.

[39]  Bechara Kachar,et al.  Have we found the tip link, transduction channel, and gating spring of the hair cell? , 2005, Current Opinion in Neurobiology.

[40]  R. Goodyear,et al.  Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear , 1992, The Journal of comparative neurology.

[41]  K. Johnson,et al.  A missense mutation in the previously undescribed gene Tmhs underlies deafness in hurry-scurry (hscy) mice , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[42]  E. Ostap,et al.  Dynamics of myo1c (myosin-ibeta ) lipid binding and dissociation. , 2002, The Journal of biological chemistry.

[43]  P. Gillespie,et al.  Myosin-1c, the hair cell's adaptation motor. , 2004, Annual review of physiology.

[44]  A J Hudspeth,et al.  Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. Goodyear,et al.  A Receptor-Like Inositol Lipid Phosphatase Is Required for the Maturation of Developing Cochlear Hair Bundles , 2003, The Journal of Neuroscience.

[46]  M G Evans,et al.  The actions of calcium on the mechano‐electrical transducer current of turtle hair cells. , 1991, The Journal of physiology.

[47]  R. Eatock,et al.  Time course and extent of mechanotransducer adaptation in mouse utricular hair cells: comparison with frog saccular hair cells. , 2003, Journal of neurophysiology.

[48]  P. Heppenstall,et al.  Direct activation of the ion channel TRPA1 by Ca2+ , 2007, Nature Neuroscience.

[49]  R. Fettiplace,et al.  The mechanical properties of ciliary bundles of turtle cochlear hair cells. , 1985, The Journal of physiology.

[50]  K. Nagata,et al.  Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing , 2005, The Journal of Neuroscience.

[51]  C. Zuker,et al.  Genetic dissection of mechanosensory transduction: Mechanoreception-defective mutations of drosophila , 1994, Neuron.

[52]  Sergei Sukharev,et al.  Mechanosensitive Channels: Multiplicity of Families and Gating Paradigms , 2004, Science's STKE.

[53]  Steve D. M. Brown,et al.  Defective myosin VIIA gene responsible for Usher syndrome type IB , 1995, Nature.

[54]  D P Corey,et al.  Kinetics of the receptor current in bullfrog saccular hair cells , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  Joe C. Adams,et al.  Localization of pH regulating proteins H+ATPase and Cl − HCO 3 − , 1997, Hearing Research.

[56]  A. Hudspeth,et al.  Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics , 1989, Hearing Research.

[57]  J. R. Holt,et al.  The Very Large G-Protein-Coupled Receptor VLGR1: A Component of the Ankle Link Complex Required for the Normal Development of Auditory Hair Bundles , 2006, The Journal of Neuroscience.

[58]  R. Goodyear,et al.  A Novel Antigen Sensitive to Calcium Chelation That is Associated with the Tip Links and Kinocilial Links of Sensory Hair Bundles , 2003, The Journal of Neuroscience.

[59]  Adenine nucleoside diphosphates block adaptation of mechanoelectrical transduction in hair cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[60]  W. Kimberling,et al.  Localization and expression of usherin: a novel basement membrane protein defective in people with Usher’s syndrome type IIa , 2002, Hearing Research.

[61]  C. Montell,et al.  Lysosomal Localization of TRPML3 Depends on TRPML2 and the Mucolipidosis-associated Protein TRPML1* , 2006, Journal of Biological Chemistry.

[62]  C. Zuker,et al.  A Drosophila mechanosensory transduction channel. , 2000, Science.

[63]  A J Hudspeth,et al.  Extracellular current flow and the site of transduction by vertebrate hair cells , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[64]  A J Hudspeth,et al.  Regulation of Free Ca2+ Concentration in Hair-Cell Stereocilia , 1998, The Journal of Neuroscience.

[65]  Makoto Tominaga,et al.  Heat-Evoked Activation of the Ion Channel, TRPV4 , 2002, The Journal of Neuroscience.

[66]  C. Cremers,et al.  Mutations in the lipoma HMGIC fusion partner‐like 5 (LHFPL5) gene cause autosomal recessive nonsyndromic hearing loss , 2006, Human mutation.

[67]  Robert Fettiplace,et al.  Tonotopic Variation in the Conductance of the Hair Cell Mechanotransducer Channel , 2003, Neuron.

[68]  Heidi L. Rehm,et al.  TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells , 2004, Nature.

[69]  D. Corey,et al.  Unconventional Myosins in Inner-Ear Sensory Epithelia , 1997, The Journal of cell biology.

[70]  The extent of adaptation in bullfrog saccular hair cells , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[71]  K. Shokat,et al.  Engineering of the Myosin-Iβ Nucleotide-binding Pocket to Create Selective Sensitivity to N 6-modified ADP Analogs* , 1999, The Journal of Biological Chemistry.

[72]  David E. Clapham,et al.  TRP channels as cellular sensors , 2003, Nature.

[73]  A J Hudspeth,et al.  Detection of Ca2+ entry through mechanosensitive channels localizes the site of mechanoelectrical transduction in hair cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[74]  C. Hackney,et al.  An immunogold investigation of the distribution of calmodulin in the apex of cochlear hair cells , 2002, Hearing Research.

[75]  A. G. Filoteo,et al.  Low Endolymph Calcium Concentrations in deafwaddler2J Mice Suggest that PMCA2 Contributes to Endolymph Calcium Maintenance , 2004, Journal of the Association for Research in Otolaryngology.

[76]  R. Goodyear,et al.  Development and properties of stereociliary link types in hair cells of the mouse cochlea , 2005, The Journal of comparative neurology.

[77]  K. Steel,et al.  Combined cochleo-saccular and neuroepithelial abnormalities in the Varitint-waddler-J (VaJ ) mouse , 1998, Hearing Research.

[78]  David M Tobin,et al.  Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Rainer W Friedrich,et al.  NompC TRP Channel Required for Vertebrate Sensory Hair Cell Mechanotransduction , 2003, Science.

[80]  C. G. Wright,et al.  A new mouse insertional mutation that causes sensorineural deafness and vestibular defects. , 1999, Genetics.

[81]  Clifford J. Woolf,et al.  TRPA1 Contributes to Cold, Mechanical, and Chemical Nociception but Is Not Essential for Hair-Cell Transduction , 2006, Neuron.

[82]  A. Hudspeth,et al.  Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[83]  J. Rigaud,et al.  Ca2+/H+ countertransport and electrogenicity in proteoliposomes containing erythrocyte plasma membrane Ca-ATPase and exogenous lipids. , 1994, The Journal of biological chemistry.

[84]  B. Kachar,et al.  High-resolution structure of hair-cell tip links. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[85]  D J DeRosier,et al.  Actin filaments, stereocilia, and hair cells: how cells count and measure. , 1992, Annual review of cell biology.

[86]  A. Hudspeth,et al.  Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor , 2000, Cell.

[87]  P. Gillespie,et al.  Regeneration of broken tip links and restoration of mechanical transduction in hair cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[88]  Richard Goodyear,et al.  The Ankle-Link Antigen: an Epitope Sensitive to Calcium Chelation Associated with the Hair-Cell Surface and the Calycal Processes of Photoreceptors , 1999, The Journal of Neuroscience.

[89]  G. Richardson,et al.  Block by amiloride and its derivatives of mechano‐electrical transduction in outer hair cells of mouse cochlear cultures. , 1994, The Journal of physiology.

[90]  Phosphate Analogs Block Adaptation in Hair Cells by Inhibiting Adaptation-Motor Force Production , 1996, Neuron.

[91]  K. Steel,et al.  Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D , 2001, Nature Genetics.

[92]  S. Schwartz,et al.  Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. , 2001, Human molecular genetics.

[93]  T. Hasson,et al.  Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[94]  D. McMillan,et al.  Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice , 2004, Molecular and Cellular Neuroscience.

[95]  R. Fettiplace,et al.  The Concentrations of Calcium Buffering Proteins in Mammalian Cochlear Hair Cells , 2005, The Journal of Neuroscience.

[96]  J. Sahel,et al.  Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. , 1996, Human molecular genetics.

[97]  A. J. Hudspeth,et al.  Ionic basis of the receptor potential in a vertebrate hair cell , 1979, Nature.

[98]  John A. Assad,et al.  Tip-link integrity and mechanical transduction in vertebrate hair cells , 1991, Neuron.

[99]  U. Wolfrum,et al.  Interactions in the network of Usher syndrome type 1 proteins. , 2005, Human molecular genetics.

[100]  A J Hudspeth,et al.  Rapid, Active Hair Bundle Movements in Hair Cells from the Bullfrog’s Sacculus , 1996, The Journal of Neuroscience.

[101]  D. Corey,et al.  TRP channels in mechanosensation , 2005, Current Opinion in Neurobiology.

[102]  D. McKemy,et al.  Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1 , 2004, Nature.

[103]  Functional expression of transient receptor potential vanilloid 4 in the mouse cochlea , 2006, Neuroreport.

[104]  A J Hudspeth,et al.  How the ear's works work: mechanoelectrical transduction and amplification by hair cells. , 2005, Comptes rendus biologies.

[105]  H. Kennedy,et al.  FM1-43 Dye Behaves as a Permeant Blocker of the Hair-Cell Mechanotransducer Channel , 2001, The Journal of Neuroscience.

[106]  Stephan C. Schuster,et al.  Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells , 2004, Nature.

[107]  Z. Ahmed,et al.  Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development. , 2005, Developmental biology.

[108]  K. Steel,et al.  Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations , 2002, Nature Neuroscience.

[109]  A. Hudspeth,et al.  Response latency of vertebrate hair cells. , 1979, Biophysical journal.

[110]  J. Pickles,et al.  Crosslinks between stereocilia in hair cells of the human and guinea pig vestibular labyrinth , 1986, The Journal of Laryngology & Otology.

[111]  D P Corey,et al.  Analysis of the microphonic potential of the bullfrog's sacculus , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[112]  M. G. Evans,et al.  Fast adaptation of mechanoelectrical transducer channels in mammalian cochlear hair cells , 2003, Nature Neuroscience.

[113]  D P Corey,et al.  Voltage dependence of adaptation and active bundle movement in bullfrog saccular hair cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[114]  A J Ricci,et al.  Two components of transducer adaptation in auditory hair cells. , 1999, Journal of neurophysiology.

[115]  G. Geleoc,et al.  A quantitative comparison of mechanoelectrical transduction in vestibular and auditory hair cells of neonatal mice , 1997, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[116]  B. Tempel,et al.  Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice , 1998, Nature Genetics.

[117]  D P Corey,et al.  Adaptation of mechanoelectrical transduction in hair cells of the bullfrog's sacculus , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[118]  J. Taube.  The head direction signal: origins and sensory-motor integration. , 2007, Annual review of neuroscience.

[119]  A J Ricci,et al.  Probing the pore of the auditory hair cell mechanotransducer channel in turtle , 2004, The Journal of physiology.

[120]  C. G. Wright,et al.  The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene , 2001, Nature Genetics.

[121]  A. Hudspeth,et al.  Plasma Membrane Ca2+-ATPase Extrudes Ca2+from Hair Cell Stereocilia , 1998, The Journal of Neuroscience.

[122]  H. Ohmori,et al.  Amiloride blocks the mechano‐electrical transduction channel of hair cells of the chick. , 1988, The Journal of physiology.

[123]  R. Goodyear,et al.  Hair and supporting‐cell differentiation during the development of the avian inner ear , 1995, The Journal of comparative neurology.

[124]  J. Gale,et al.  Mechano-electrical Transduction: New Insights into Old Ideas , 2006, The Journal of Membrane Biology.

[125]  Elyssa B. Margolis,et al.  Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. , 2007, Annual review of neuroscience.

[126]  J. O. Pickles,et al.  Cross-links between stereocilia in the guinea pig organ of Corti, and their possible relation to sensory transduction , 1984, Hearing Research.

[127]  K. D. Karavitaki,et al.  HAIR BUNDLE MECHANICS AT HIGH FREQUENCIES: A TEST OF SERIES OR PARALLEL TRANSDUCTION , 2006 .

[128]  D. Corey,et al.  Localization of Myosin-Iβ near Both Ends of Tip Links in Frog Saccular Hair Cells , 1998, The Journal of Neuroscience.

[129]  J. Ruppersberg,et al.  Mechanically and ATP-induced currents of mouse outer hair cells are independent and differentially blocked by d-tubocurarine , 1997, Neuropharmacology.

[130]  S. Riazuddin,et al.  Mutations of human TMHS cause recessively inherited non-syndromic hearing loss , 2006, Journal of Medical Genetics.

[131]  G. Shepherd,et al.  "Bundle blot" purification and initial protein characterization of hair cell stereocilia. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[132]  R. Rao,et al.  Vestibular Hair Bundles Control pH with (Na+, K+)/H+ Exchangers NHE6 and NHE9 , 2006, The Journal of Neuroscience.

[133]  J. Cotton,et al.  Computational models of hair cell bundle mechanics: II. Simplified bundle models , 2004, Hearing Research.

[134]  A. Griffith,et al.  Genetic insights into the morphogenesis of inner ear hair cells , 2004, Nature Reviews Genetics.

[135]  C. Kros,et al.  The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano 
‐electrical transducer channels , 2005, The Journal of physiology.

[136]  A J Ricci,et al.  The effects of calcium buffering and cyclic AMP on mechano‐electrical transduction in turtle auditory hair cells , 1997, The Journal of physiology.

[137]  A. J. Hudspeth,et al.  Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the Bullfrog's saccular hair cell , 1988, Neuron.

[138]  P. Gillespie,et al.  Xenopus TRPN1 (NOMPC) localizes to microtubule-based cilia in epithelial cells, including inner-ear hair cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[139]  Bernd Nilius,et al.  Permeation and selectivity of TRP channels. , 2006, Annual review of physiology.

[140]  K. Steel,et al.  A type VII myosin encoded by the mouse deafness gene shaker-1 , 1995, Nature.

[141]  Kavita Shah,et al.  A Chemical-Genetic Strategy Implicates Myosin-1c in Adaptation by Hair Cells , 2002, Cell.

[142]  K. Schulten,et al.  In search of the hair-cell gating spring elastic properties of ankyrin and cadherin repeats. , 2005, Structure.

[143]  Winfried Denk,et al.  Calcium imaging of single stereocilia in hair cells: Localization of transduction channels at both ends of tip links , 1995, Neuron.