How the Genetics of Deafness Illuminates Auditory Physiology

Abstract

Although the basic principles underlying the function of the peripheral auditory system have been known for many years, the molecules required for hearing have hitherto remained elusive. Genetic approaches have recently provided unparalleled molecular insight into how the hair bundle, the hair cell's mechanosensory organelle, forms and functions. We discuss how the proteins encoded by the Usher syndrome type 1 genes form molecular complexes required for hair-bundle development and for gating the mechanotransducer channel. We show how mouse models for nonsyndromic forms of deafness involving genes encoding Triobp and stereocilin reveal, respectively, the way stereocilia rootlets contribute to the hair bundle's mechanical properties and how the hair bundle produces suppressive masking, a property that contributes to speech intelligibility. Finally, we examine how mutations in the genes encoding α- and β-tectorin reveal multiple roles for the tectorial membrane, an extracellular matrix unique to the cochlea, in stimulating hair bundles.