Cochlear supporting cells require GAS2 for cytoskeletal architecture and hearing

In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea.

Automated summary

In mammals, sound is detected by mechanosensory hair cells, with inner ear supporting cells playing a crucial role in transmitting sound energy through the cochlear partition. Mutations in the GAS2 gene can lead to hearing loss by disrupting the organization and stability of microtubule bundles in these supporting cells, affecting cochlear micromechanics. The bundling activity of GAS2 is essential for imparting mechanical properties to supporting cells for sound energy transmission in the cochlea.