المؤلفون: Emily R. Towers, Jonathan E. Gale, Sally J. Dawson, John J. Kelly, Richa Sud

المصدر: Journal of Cell Science. 124:1145-1155

مصطلحات موضوعية: Hearing loss, Down-Regulation, Cell Cycle Proteins, Deafness, Biology, Cell Line, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Stress granule, Downregulation and upregulation, Cellular stress response, otorhinolaryngologic diseases, medicine, Animals, Humans, Transcription factor, Cells, Cultured, Research Articles, Cochlea, 030304 developmental biology, Homeodomain Proteins, Genetics, 0303 health sciences, Hair Cells, Auditory, Inner, Transcription Factor Brn-3C, Cell Biology, Anti-Bacterial Agents, Rats, Cell biology, Aminoglycosides, medicine.anatomical_structure, sense organs, Hair cell, medicine.symptom, 030217 neurology & neurosurgery, Protein Binding

الوصف: The POU4 family of transcription factors are required for survival of specific cell types in different sensory systems. Pou4f3 is essential for the survival of auditory sensory hair cells and several mutations in human POU4F3 cause hearing loss. Thus, genes regulated by Pou4f3 are likely to be essential for hair cell survival. We performed a subtractive hybridisation screen in an inner-ear-derived cell line to find genes with differential expression in response to changes in Pou4f3 levels. The screen identified the stress-granule-associated protein Caprin-1 as being downregulated by Pou4f3. We demonstrated that this regulation occurs through the direct interaction of Pou4f3 with binding sites in the Caprin-1 5′ flanking sequence, and describe the expression pattern of Caprin-1 mRNA and protein in the cochlea. Moreover, we found Caprin-1-containing stress granules are induced in cochlear hair cells following aminoglycoside-induced damage. This is the first report of stress granule formation in mammalian hair cells and suggests that the formation of Caprin-1-containing stress granules is a key damage response to a clinically relevant ototoxic agent. Our results have implications for the understanding of aminoglycoside-induced hearing loss and provide further evidence that stress granule formation is a fundamental cellular stress response.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f9ba32ddf74a1ad1686a5722bd9bbfc
https://doi.org/10.1242/jcs.076141