Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Müller, U. et al. Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature 449, 87-91

The Scripps Research, Institute Department of Cell Biology, La Jolla, California 92037, USA.
Nature (Impact Factor: 41.46). 10/2007; 449(7158):87-91. DOI: 10.1038/nature06091
Source: PubMed


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 channel. Recent reports on the composition, properties and function of tip links are conflicting. Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans 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 deafness 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.

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Available from: Elizabeth M Wilson-Kubalek
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    • "ween adhesion domains ( Sackmann and Smith , 2014 ) . Inter - estingly , however , the geometry of intermediate contacts sug - gests that they mediate adhesion , and lanthanum / alcian blue staining is consistent with an adhesive ECM or glycocalyx . However , we cannot exclude cell – cell attachment by very large nonclassical cadherins ( e . g . , Kazmierczak et al . , 2007 ) . Cell – ECM adhesion is common , but cell – cell adhesion mediated by an intervening thin layer of ECM is not well described other than in sponges , where large extracellular proteoglycan com - plexes are bound by cell surface receptors ( Bucior and Burger , 2004 ; Bucior et al . , 2004 ) . Nonetheless , the combination of facilitate"
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