期刊
JOURNAL OF NEUROSCIENCE
卷 37, 期 13, 页码 3447-3464出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2711-16.2017
关键词
auditory neuropathy spectrum disorder; DFNB59; hair cell; hearing loss; inner ear; pejvakin
资金
- National Institutes of Health [DC013331, DC003896, DC013299]
- Rutgers State University of New Jersey
- Busch Biomedical Grant to M.S
- Capita Foundation for Hearing Research Fellowship
- National Institute on Deafness and Other Communication Disorders [DC014713, DC007704]
- Inserm [U1051-Dot 02]
- Fondation Gueules [09-2014]
- Montpellier University postdoctoral fellowship
Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function.
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