Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice

Rzadzinska, Agnieszka K.; Derr, Adam; Kachar, Bechara; Noben-Trauth, Konrad

doi:10.1016/j.heares.2005.05.008

Cited by 35 publications

(31 citation statements)

References 29 publications

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“…Espin can be detected in hair bundles shortly after they have first emerged (Li et al, 2004) and espin levels in mature hair bundles correlate with hair-bundle length (Loomis et al, 2003). Levels of espin expression have been experimentally shown to regulate the length of microvilli in cultured epithelial cells (Loomis et al, 2003) and the overexpression of espin in cochlear hair cells causes a lengthening of the hair bundle (Rzadzinska et al, 2005). The over-expression of espin in cochlear supporting cells can lead to the appearance of structures that resemble hair bundles.…”

Section: Actin Cross Linkersmentioning

confidence: 99%

Development of the hair bundle and mechanotransduction

Nayak

Ratnayaka²,

Goodyear³

et al. 2007

Int. J. Dev. Biol.

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This review focuses on the cellular and molecular mechanisms underlying the development of the sensory hair bundle, an apical specialisation of the hair cell that is essential for mechanotransduction. The structure, function and development of the hair bundle is described, with an emphasis on the properties and possible roles played by the different link types that interconnect the individual elements of the hair bundle -the multiple stereocilia and the single kinocilium. Studies of mouse and zebrafish mutants have revealed that several classes of molecule are required for the genesis and maintenance of hair-bundle structure. These include cell surface molecules that are associated with the different hair-bundle links, along with myosin motors, scaffolding proteins and an actin cross-linker. Finally we consider how differences in the form and shape of hair bundles within and between different sensory organs are generated.

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Section: Actin Cross Linkersmentioning

confidence: 99%

Development of the hair bundle and mechanotransduction

Nayak

Ratnayaka²,

Goodyear³

et al. 2007

Int. J. Dev. Biol.

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“…Lagziel and T. Friedman, personal communication). Moreover, other antibodies against the C terminus do not detect Cdh23 protein in cochleas of Cdh23 v2J homozygous mice by immunoblotting (Rzadzinska et al, 2005). To further characterize the hair bundles of the Cdh23 v2J , we first examined the localization of endogenous Myo1c in cochleas of both Cdh23 v2J heterozygous and homozygous mice.…”

Section: Interaction Of Myo1c-t701 and Stereociliary Receptors Does Nmentioning

confidence: 99%

“…Stereocilia are interconnected by several types of extracellular linkages including the tip link, which connects the top of a shorter stereocilium to the side of its tallest neighbor (Pickles et al, 1984). Cadherin 23 (Cdh23) has been proposed to be a tiplink component (Siemens et al, 2004;Söllner et al, 2004); however, this designation is controversial (Lagziel et al, 2005;Michel et al, 2005;Rzadzinska et al, 2005). In the prevailing model of hair-cell transduction, bundle deflection tenses tip links and opens mechanically gated, cation-selective transduction channels (Pickles et al, 1984;Howard and Hudspeth, 1987).…”

Section: Introductionmentioning

confidence: 99%

Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice

Phillips

Tong²,

Goodyear³

et al. 2006

J. Neurosci.

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The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP 2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP 2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM.

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“…CDH23 and PCDH15 are components of transient lateral links, kinociliary links, and tip links ( Fig. 1 A) (16)(17)(18)(19)(20), and their cytoplasmic domains bind to protein complexes containing harmonin, MYO7A, and sans (21)(22)(23)(24)(25). Predicted null mutations in murine USH1 genes cause defects in hair bundle development (24,(26)(27)(28)(29)(30)(31)(32)(33)(34), suggesting that USH1 proteins form transmembrane complexes that regulate hair bundle morphogenesis.…”

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confidence: 99%

A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells

Schwander

Xiong

Tokita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Deafness is the most common form of sensory impairment in humans and is frequently caused by single gene mutations. Interestingly, different mutations in a gene can cause syndromic and nonsyndromic forms of deafness, as well as progressive and age-related hearing loss. We provide here an explanation for the phenotypic variability associated with mutations in the cadherin 23 gene (CDH23). CDH23 null alleles cause deaf-blindness (Usher syndrome type 1D; USH1D), whereas missense mutations cause nonsyndromic deafness (DFNB12). In a forward genetic screen, we have identified salsa mice, which suffer from hearing loss due to a Cdh23 missense mutation modeling DFNB12. In contrast to waltzer mice, which carry a CDH23 null allele mimicking USH1D, hair cell development is unaffected in salsa mice. Instead, tip links, which are thought to gate mechanotransduction channels in hair cells, are progressively lost. Our findings suggest that DFNB12 belongs to a new class of disorder that is caused by defects in tip links. We propose that mutations in other genes that cause USH1 and nonsyndromic deafness may also have distinct effects on hair cell development and function.cadherin 23 ͉ Cdh23 ͉ Usher syndrome ͉ progressive hearing loss

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Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice

Cited by 35 publications

References 29 publications

Development of the hair bundle and mechanotransduction

Development of the hair bundle and mechanotransduction

Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice

A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells

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