Cochlear supporting cells require GAS2 for cytoskeletal architecture and hearing

Tingfang Chen, Alex M. Rohacek, Matthew Caporizzo, Amir Nankali, Jeroen J. Smits, Jaap Oostrik, Cornelis P. Lanting, Erdi Kücük, Christian Gilissen, Jiddeke M. van de Kamp, Ronald J.E. Pennings, Staci M. Rakowiecki, Klaus H. Kaestner, Kevin K. Ohlemiller, John S. Oghalai, Hannie Kremer, Benjamin L. Prosser, Douglas J. Epstein

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1526-1540.e7
JournalDevelopmental cell
Volume56
Issue number10
DOIs
StatePublished - May 17 2021

Keywords

  • Gas2
  • cochlea
  • cochlear mechanics
  • cytoskeleton
  • hearing loss
  • microtubules
  • supporting cells

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