The composition and role of cross links in mechanoelectrical transduction in vertebrate sensory hair cells

Abstract

SummaryThe key components of acousticolateralis systems (lateral line, hearing and balance) are sensory hair cells. At their apex, these cells have a bundle of specialized cellular protrusions, which are modified actin-containing microvilli, connected together by extracellular filaments called cross links. Stereociliary deflections open nonselective cation channels allowing ions from the extracellular environment into the cell, a process called mechanoelectrical transduction. This produces a receptor potential that causes the release of the excitatory neurotransmitter glutamate onto the terminals of the sensory nerve fibres, which connect to the cell base, causing nerve signals to be sent to the brain. Identification of the cellular mechanisms underlying mechanoelectrical transduction and of some of the proteins involved has been assisted by research into the genetics of deafness, molecular biology and mechanical measurements of function. It is thought that one type of cross link, the tip link, is composed of cadherin 23 and protocadherin 15, and gates the transduction channel when the bundle is deflected. Another type of link, called lateral (or horizontal) links, maintains optimal bundle cohesion and stiffness for transduction. This Commentary summarizes the information currently available about the structure, function and composition of the links and how they might be relevant to human hearing impairment.

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

“…These interstereociliary links are essential for bundle development, maintenance and function [75–77]. During early development, kinociliary links connect the kinocilium to its neighboring stereocilia, and transient lateral links connect adjacent stereocilia along their entire length [75, 76]. Later, ankle links and tip links emerge at the stereociliary base and tip, respectively [76].…”

“…Electron dense structures, upper (UTLD) and lower (LTLD) tip link densities (Figure 3), are observed at the upper and lower insertion sites of tip links in stereocilia, respectively. Kinociliary links, transient lateral links and ankle links disappear after maturation of mammalian cochlear hair cells, but some are permanent in the vestibular system [75, 76]. Tip links remain in mature cochlear and vestibular hair cells throughout life [78, 79].…”

Abstracts of the Fourth Joint Annual Conference, Experimental and Clinical Short Papers Meetings of the British Society of Audiology

“…Furness . Institute for Science and Technology in Medicine, Keele University, UK The hair bundle of vertebrate hair cells contains precisely arranged stereocilia forming rows that increase in height like a staircase, connected together by fi ne fi lamentous structures, the tip links and lateral links (see review by Hackney & Furness, 2013). Whilst the tip link is morphologically distinct, lateral links have also been subdivided into categories: top connectors (between the tips of adjacent tall stereocilia and also from the tips of shorter stereocilia to tall stereocilia), shaft links (occurring below the tips), and ankle links (where the stereocilia narrow).…”

Transcription factors in the development of inner ear hair cells

“…Several transcription factors participate in regulating the development of the inner ear, even from the embryonic stage (2-7). Among the various types of cells in the inner ear, hair cells are the sensory receptors that detect and convert sound vibrations and head movements into neural signals (8,9). However, hair (10).…”