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Cover  This month's cover illustration shows images and a diagram of a key element in auditory and vestibular sensory cells, the tip link. The auditory and vestibular sensory systems rely on a direct mechanical gating of their transduction channels. This gating mechanism is located on the tips of stereocilia, which are arranged in a bundle on the sensory cell apex (left panel). Bundle deflection stretches elastic elements, the gating springs, which transmit force to the hundred or so transduction channels per cell (Hudspeth AJ [1989]. Nature 341, 397-404). The best candidate for the gating spring is the tip link, an extracellular filament that joins a stereocilium to its tallest neighbor, parallel to the bundle's axis of mechanical sensitivity (Pickles et al. [1985]. Hearing Res. 18, 177-188).

To determine whether the tip link could be the gating spring, Kachar et al. (PNAS, [2000]. 97, 13336-13341) examined its structure at high resolution using rapid-freeze, deep-etching electron microscopy with improved metal-replication and imaging procedures. The deep-etching replicas (middle panel) showed that the tip link is a right-handed, 8- to 10-nm coiled double filament that usually forks into two branches before contacting a taller stereocilium; at the other end, several short filaments extend to the tip link from the shorter stereocilium. The structure of the tip link suggests that it is either a helical polymer or a braided pair of filamentous macromolecules and is therefore likely to be relatively stiff and inextensible. The proposed inextensibility of the tip link suggests that yet another elastic element within the hair bundle must be the true gating spring, and that the tip link instead connects to it in series to direct force to the channel.

Because tips links are so scarce and difficult to assay, conventional methods for identification and characterization of biological macromolecules cannot be readily applied to them. Structural determination with electron microscopy as shown in this study does, however, allow description of properties of the tip link that may assist in identification of its molecular constituents.Bechara Kachar