Reproduced, with permission, from Siemens et al., Nature © (2004) Macmillan Magazines Ltd.

The hair cells of the inner ear provide a mechanosensory mechanism that converts mechanical stimuli into electrochemical signals. Each hair cell is topped by a bundle of stereocilia, which are linked together at their tips. When the stereocilia are deflected by a sound or head movement, tension is generated in the tip links. This causes mechanotransduction channels at either end of the link to open, allowing ions to flow into the cell. Little was known about the chemical composition of the tip links, but two groups have recently reported in Nature that the adhesion molecule cadherin 23 (Cdh23) is one of the main constituents.

It was previously thought that Cdh23 was lost from stereocilia as the hair cells become mature, but Siemens et al. were able to detect Cdh23-coding messenger RNAs in the inner ears of adult mice. The protein itself was localized to the tips of stereocilia, and using immunoelectron microscopy, the authors pinpointed its location to the tip link. They also showed that the tip link could be severed by agents that disrupt the adhesive functions of Cdh23, and that Cdh23 interacts with myosin-1c, another component of the mechanotransduction apparatus.

Mutations in the Cdh23 gene have been shown to cause deafness and balance problems in mice and humans. The zebrafish sputnik mutant shows a similar phenotype, and in the second study, Söllner et al. showed that the sputnik gene codes for Cdh23. The authors examined the hair cells in the sputnik mutant, and they found that the stereocilia were frequently splayed out rather than bundled together.

The discovery that Cdh23 is a crucial component of the tip link has important ramifications for our understanding of the inner ear's mechanotransduction mechanism. The mechanotransduction channels seem be gated by a spring-like structure, which was suggested to be the tip link itself. However, Cdh23 filaments are unlikely to be sufficiently stretchy to carry out this function. In a News and Views article, Corey and Sotomayor propose a new model, in which the gating spring is an integral part of the channel. In support of this model, an ion channel that has been implicated in mechanotransduction in zebrafish has been shown to contain ankyrin repeats, which form a helical structure that is predicted to have spring-like properties.