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Genetics of auditory mechano-electrical transduction.

Michalski N, Petit C - Pflugers Arch. (2014)

Bottom Line: The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea.Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current.Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France, nicolas.michalski@pasteur.fr.

ABSTRACT
The hair bundles of cochlear hair cells play a central role in the auditory mechano-electrical transduction (MET) process. The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea. In contrast, human and mouse genetics have proven to be particularly powerful. The study of inherited forms of deafness led to the discovery of several essential proteins of the MET machinery, which are currently used as entry points to decipher the associated molecular networks. Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current. Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

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Related in: MedlinePlus

Hair bundle cohesion. Top Schematic illustration of the different types of links between stereocilia in OHCs at three different developmental stages, E17.5, P5, and P14. Bottom Molecular composition of the different links and their associated molecular complexes. Single asterisk The positions of the listed proteins at the upper or lower tip-link insertion points are detailed in Fig. 5. Double asterisk Usherin and PTPRQ are part of the ankle link complex and the shaft link complex, respectively, but it is unknown whether these proteins form the links
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Fig3: Hair bundle cohesion. Top Schematic illustration of the different types of links between stereocilia in OHCs at three different developmental stages, E17.5, P5, and P14. Bottom Molecular composition of the different links and their associated molecular complexes. Single asterisk The positions of the listed proteins at the upper or lower tip-link insertion points are detailed in Fig. 5. Double asterisk Usherin and PTPRQ are part of the ankle link complex and the shaft link complex, respectively, but it is unknown whether these proteins form the links

Mentions: The formation of the hair bundle and the maintenance of its cohesiveness are orchestrated by several types of links that come into play at different developmental stages. Prior to their molecular description, these links were categorised according to both their location and sensitivity to proteases/calcium chelators (Fig. 3) [19, 75]. In the newborn mouse (P0), numerous interstereociliary lateral links interconnect stereocilia across and between rows in different directions. From P2 onwards, three types of lateral links take over, namely ankle links that are located at the base of stereocilia and shaft connectors that are located along stereocilia, and kinocilial links that connect the kinocilium to adjacent stereocilia of the tallest row. In mature cochlear hair cells, only the tip links remain, together with putative lateral links in IHCs and apical top connectors in OHCs [75]. Several molecular components of these links have been identified (see Table 1). Mutations in the corresponding genes in mice lead to congenital hearing impairment and hair-bundle disorganisation, indicating that each link type contributes critically to the building or the maintenance of the hair bundle.Fig. 3


Genetics of auditory mechano-electrical transduction.

Michalski N, Petit C - Pflugers Arch. (2014)

Hair bundle cohesion. Top Schematic illustration of the different types of links between stereocilia in OHCs at three different developmental stages, E17.5, P5, and P14. Bottom Molecular composition of the different links and their associated molecular complexes. Single asterisk The positions of the listed proteins at the upper or lower tip-link insertion points are detailed in Fig. 5. Double asterisk Usherin and PTPRQ are part of the ankle link complex and the shaft link complex, respectively, but it is unknown whether these proteins form the links
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4281357&req=5

Fig3: Hair bundle cohesion. Top Schematic illustration of the different types of links between stereocilia in OHCs at three different developmental stages, E17.5, P5, and P14. Bottom Molecular composition of the different links and their associated molecular complexes. Single asterisk The positions of the listed proteins at the upper or lower tip-link insertion points are detailed in Fig. 5. Double asterisk Usherin and PTPRQ are part of the ankle link complex and the shaft link complex, respectively, but it is unknown whether these proteins form the links
Mentions: The formation of the hair bundle and the maintenance of its cohesiveness are orchestrated by several types of links that come into play at different developmental stages. Prior to their molecular description, these links were categorised according to both their location and sensitivity to proteases/calcium chelators (Fig. 3) [19, 75]. In the newborn mouse (P0), numerous interstereociliary lateral links interconnect stereocilia across and between rows in different directions. From P2 onwards, three types of lateral links take over, namely ankle links that are located at the base of stereocilia and shaft connectors that are located along stereocilia, and kinocilial links that connect the kinocilium to adjacent stereocilia of the tallest row. In mature cochlear hair cells, only the tip links remain, together with putative lateral links in IHCs and apical top connectors in OHCs [75]. Several molecular components of these links have been identified (see Table 1). Mutations in the corresponding genes in mice lead to congenital hearing impairment and hair-bundle disorganisation, indicating that each link type contributes critically to the building or the maintenance of the hair bundle.Fig. 3

Bottom Line: The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea.Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current.Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France, nicolas.michalski@pasteur.fr.

ABSTRACT
The hair bundles of cochlear hair cells play a central role in the auditory mechano-electrical transduction (MET) process. The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea. In contrast, human and mouse genetics have proven to be particularly powerful. The study of inherited forms of deafness led to the discovery of several essential proteins of the MET machinery, which are currently used as entry points to decipher the associated molecular networks. Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current. Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

Show MeSH
Related in: MedlinePlus