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dc.contributor.authorBlanco-Sánchez, Bernardo  Concept link
dc.contributor.authorClément, Aurélie  Concept link
dc.contributor.authorFierro, Javier  Concept link
dc.contributor.authorStednitz, Sarah  Concept link
dc.contributor.authorPhillips, Jennifer B.  Concept link
dc.contributor.authorWegner, Jeremy  Concept link
dc.contributor.authorPanlilio, Jennifer M.  Concept link
dc.contributor.authorPeirce, Judy L.  Concept link
dc.contributor.authorWashbourne, Philip  Concept link
dc.contributor.authorWesterfield, Monte  Concept link
dc.identifier.citationCell Reports 25 (2018): 1281–1291en_US
dc.description© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cell Reports 25 (2018): 1281–1291, doi:10.1016/j.celrep.2018.10.005.en_US
dc.description.abstractMorphogenesis and mechanoelectrical transduction of the hair cell mechanoreceptor depend on the correct assembly of Usher syndrome (USH) proteins into highly organized macromolecular complexes. Defects in these proteins lead to deafness and vestibular areflexia in USH patients. Mutations in a non-USH protein, glutaredoxin domain-containing cysteine-rich 1 (GRXCR1), cause non-syndromic sensorineural deafness. To understand the deglutathionylating enzyme function of GRXCR1 in deafness, we generated two grxcr1 zebrafish mutant alleles. We found that hair bundles are thinner in homozygous grxcr1 mutants, similar to the USH1 mutants ush1c (Harmonin) and ush1ga (Sans). In vitro assays showed that glutathionylation promotes the interaction between Ush1c and Ush1ga and that Grxcr1 regulates mechanoreceptor development by preventing physical interaction between these proteins without affecting the assembly of another USH1 protein complex, the Ush1c- Cadherin23-Myosin7aa tripartite complex. By elucidating the molecular mechanism through which Grxcr1 functions, we also identify a mechanism that dynamically regulates the formation of Usher protein complexes.en_US
dc.description.sponsorshipThis work was supported by grants from the NIH (DC004186, OD011195, and HD22486).en_US
dc.publisherCell Pressen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectUsher syndromeen_US
dc.subjectHair cellen_US
dc.titleGrxcr1 promotes hair bundle development by destabilizing the physical interaction between Harmonin and Sans usher syndrome proteinsen_US

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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International