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Journal Articles EMBO Molecular Medicine Year : 2019

Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

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Sara Wells
Michael R Bowl
  • Function : Correspondent author
  • PersonId : 1102212

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Abstract

Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, genome mapping and gene complementation tests, we identified Clrn2 as a new deafness gene. The Clrn2 clarinet/clarinet mice (p.Trp4* mutation) exhibit a progressive, early-onset hearing loss, with no overt retinal deficits. Utilizing data from the UK Biobank study, we could show that CLRN2 is involved in human non-syndromic progressive hearing loss. Our indepth morphological, molecular and functional investigations establish that while it is not required for initial formation of cochlear sensory hair cell stereocilia bundles, clarin-2 is critical for maintaining normal bundle integrity and functioning. In the differentiating hair bundles, lack of clarin-2 leads to loss of mechano-electrical transduction, followed by selective progressive loss of the transducing stereocilia. Together, our findings demonstrate a key role for clarin-2 in mammalian hearing, providing insights into the interplay between mechano-electrical transduction and stereocilia maintenance.
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Origin : Publication funded by an institution

Dates and versions

pasteur-03261798 , version 1 (16-06-2021)

Licence

Attribution - CC BY 4.0

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Lucy A Dunbar, Pranav Patni, Carlos Aguilar, Philomena Mburu, Laura Corns, et al.. Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function. EMBO Molecular Medicine, 2019, 11 (9), pp.e10288. ⟨10.15252/emmm.201910288⟩. ⟨pasteur-03261798⟩
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