We study these channels primarily in vertebrate hair cells -- the receptor cells of the inner ear, which are sensitive to sounds or accelerations. Hair cells are epithelial cells, with a bundle of stereocilia rising from their apical surfaces. Mechanical deflection of the bundles changes the tension in fine "tip links" that stretch between the stereocilia; these filaments are thought to pull directly on the mechanically gated transduction channels to regulate their opening. Tip links are made of two unusual cadherins with long extracellular domains--cadherin 23 and protocadherin 15—whose N-termini join to complete the link. We are interested in the tip link’s biophysical properties and how the two cadherins join. We have determined the crystal structure of the N-termini of protocadherin 15 bound to cadherin-23, and have used steered molecular dynamics to determine the elastic properties and unbinding force of the cadherins. The crystal structures and molecular dynamics together have helped explain how deafness-producing mutations in the tip link disrupt its structure. (Sotomayor et al., 2010; 2012)

 Cell Biology of Neurons & Glia Development & Plasticity Gene Expression  Neuropathology & Disease  Neuropharmacology & Neurochemistry  Receptors & Ion Channels Synapse Function & Plasticity  Systems & Integrative Neuroscience