Grxcr1 promotes hair bundle development by destabilizing the physical interaction between Harmonin and Sans usher syndrome proteins
Phillips, Jennifer B.
Panlilio, Jennifer M.
Peirce, Judy L.
MetadataShow full item record
Morphogenesis 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.
© 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.
Suggested CitationCell Reports 25 (2018): 1281–1291
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
Showing items related by title, author, creator and subject.
Carmack, Eddy C.; Polyakov, Igor V.; Padman, Laurie; Fer, Ilker; Hunke, Elizabeth C.; Hutchings, Jennifer K.; Jackson, Jennifer M.; Kelley, Daniel E.; Kwok, Ron; Layton, Chantelle; Melling, Humfrey; Perovich, Donald K.; Persson, Ola; Ruddick, Barry R.; Timmermans, Mary-Louise; Toole, John M.; Ross, Tetjana; Vavrus, Steve; Winsor, Peter (American Meteorological Society, 2015-12)The loss of Arctic sea ice has emerged as a leading signal of global warming. This, together with acknowledged impacts on other components of the Earth system, has led to the term “the new Arctic.” Global coupled climate ...
Distribution of postsynaptic density (PSD)-95 and Ca2+/calmodulin-dependent protein kinase II at the PSD Petersen, Jennifer D.; Chen, Xiaobing; Vinade, Lucia; Dosemeci, Ayse; Lisman, John E.; Reese, Thomas S. (Society for Neuroscience, 2003-12-03)Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We determined the positions of calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95 within the three-dimensional structure ...
Gemmell, Brad J.; Fogerson, Stephanie M.; Costello, John H.; Morgan, Jennifer R.; Dabiri, John O.; Colin, Sean P. (Company of Biologists, 2016-12-14)Swimming animals commonly bend their bodies to generate thrust. For undulating animals such as eels and lampreys, their bodies bend in the form of waves that travel from head to tail. These kinematics accelerate the flow ...