Topic
Tip link
About: Tip link is a research topic. Over the lifetime, 200 publications have been published within this topic receiving 19933 citations.
Papers published on a yearly basis
Papers
TL;DR: Hair cells, the primary receptors of the auditory, vestibular, and lateral-line sensory systems, produce electrical signals in response to mechanical stimulation of their apical hair bundles, and action potentials, possibly calcium spikes, were occasionally evoked in hair cells by mechanical or electrical stimulation.
Abstract: Hair cells, the primary receptors of the auditory, vestibular, and lateral-line sensory systems, produce electrical signals in response to mechanical stimulation of their apical hair bundles. We employed an in vitro preparation and intracellular recording to investigate the transduction mechanism of hair cells in the sacculus from the inner ear of the bullfrog (Rana catesbeiana). When stimulated directly by mechanical deflection of their hair bundles, these cells gave graded responses up to 15 mV in amplitude; the peak sensitivity was about 20 mV/micron deflection. The depolarizing component of the receptor potential corresponding to stimuli directed towards the kinocilium. Depolarizing responses were associated with a membrane resistance decrease, and hyperpolarizing responses with a resistance increase. Action potentials, possibly calcium spikes, were occasionally evoked in hair cells by mechanical or electrical stimulation.
801 citations
TL;DR: The studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.
Abstract: Hair cells of the inner ear are so-called because of the hair-like projections, or stereocilia, that protrude from their apical surface. Sound-induced stereocilial motion is thought to be coupled to mechanoelectrical transduction channels via the 'tip links' that connect stereocilia to one another. Kazmierczak et al. now report the composition of mammalian tip links. They are formed by the interaction of two members of the family of calcium-dependent cell adhesion proteins, cadherin and protocadherin 15. Interestingly, mutation of these cadherins causes deafness in humans and one such mutation disrupts the interaction between the two molecules. Hair cells of the inner ear have stereocilia that protrude from their apical surface. Sound-induced stereocilial motion is thought to be coupled to mechanoelectrical transduction channels by means of the 'tip links' that connect stereocilia to one another. This paper reports the composition of mammalian tip links cadherin 23 and protocadherin 15 and show how the two molecules interact. Interestingly, mutation of these cadherins causes deafness in humans. Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electrochemical signals to provide our sense of hearing and balance. Each hair cell contains at the apical surface a bundle of stereocilia. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel1,2,3. Recent reports on the composition4,5,6,7,8, properties and function9,10,11 of tip links are conflicting29. Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans12,13,14,15 interact to form tip links. Immunohistochemical studies using rodent hair cells show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) localize to the upper and lower part of tip links, respectively. The amino termini of the two cadherins co-localize on tip-link filaments. Biochemical experiments show that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affect tip-link integrity and a mutation in PCDH15 that causes a recessive form of deafness16 disrupt interactions between CDH23 and PCDH15. Our studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.
748 citations
TL;DR: Hair cells of the guinea pig cochlea were preserved by fixing in glutaraldehyde without the use of osmium to explain the V shape of the rows of stereocilia on outer hair cells, and a membrane roughness was seen, particularly pronounced in the region of the stereocilium which gives rise to the cross-links.
718 citations
TL;DR: The magnitude and displacement dependence of the gating compliance provide quantitative information about the molecular basis of mechanoelectrical transduction: the force required to open each channel, the number of transduction channels per hair cell, the stiffness of a gating spring, and the swing of a channel's gate as it opens.
679 citations
TL;DR: The dependences of the response kinetics on displacement and on temperature suggest that the thermal interconversion between open and closed transduction channels is limited by an enthalpy of activation of about 12 kcal/mol.
Abstract: The receptor current of hair cells from the bullfrog's sacculus was measured by voltage clamp recording across the isolated sensory epithelium. Several hundred hair cells were stimulated en masse by moving the overlying otolithic membrane with a piezoelectrically activated probe. As measured by optical recording of otolithic membrane motion, the step displacement stimuli reached their final amplitudes of up to 1 micrometer within 100 microseconds. The relationship between displacement and steady-state receptor current is an asymmetric, sigmoidal curve about 0.5 micrometer in extent. The time constant of the approach to steady state depends upon the magnitude of the hair bundle displacement and ranges from 100 to 500 microseconds at 4 degrees C; the time course is faster with larger displacements or at higher temperatures. Both the displacement-response curve and the kinetics of the response are changed by alterations in the Ca2+ concentration at the apical surface of the cells. The characteristics of the response are not consistent with simple models for the transduction process that involve enzymatic regulation of channel proteins or diffusible second messengers. Mechanical stimulation is instead posited to act directly by altering the free energy difference between the open and closed forms of the transduction channel, thereby inducing a redistribution between these states. The dependences of the response kinetics on displacement and on temperature suggest that the thermal interconversion between open and closed transduction channels is limited by an enthalpy of activation of about 12 kcal/mol.
569 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2020 | 3 |
| 2019 | 15 |
| 2018 | 12 |
| 2017 | 7 |
| 2016 | 5 |