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Publication Detail
Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Towers ER, Kelly JJ, Sud R, Gale JE, Dawson SJ
  • Publisher:
    The Company of Biologists
  • Publication date:
    03/2011
  • Place of publication:
    UK
  • Journal:
    Journal of Cell Science
  • Volume:
    124
  • Issue:
    6
  • Status:
    Accepted
  • Print ISSN:
    0021-9533
  • Language:
    English
  • EISSN:
    1477-9137
  • Keywords:
    stress granules, hair cells, aminoglycoside, cochlea, hearing
Abstract
The POU4 family of transcription factors are required for survival of specific cell types in different sensory systems. Pou4f3 is critical 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 down-regulated by Pou4f3. We demonstrate that this regulation occurs via 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 find 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 the formation of Caprin-1-containing stress granules is a key hair cell 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.
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