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The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death
Sensory hair cells are susceptible to numerous insults, including certain therapeutic medications like aminoglycoside antibiotics, and hearing and balance disorders are often a dose-limiting side effect of these medications. We show that mutations in multiple genes in both the retrograde intraflagel...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361216/ https://www.ncbi.nlm.nih.gov/pubmed/30578252 http://dx.doi.org/10.1242/bio.038745 |
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author | Stawicki, Tamara M. Linbo, Tor Hernandez, Liana Parkinson, Lauren Bellefeuille, Danielle Rubel, Edwin W. Raible, David W. |
author_facet | Stawicki, Tamara M. Linbo, Tor Hernandez, Liana Parkinson, Lauren Bellefeuille, Danielle Rubel, Edwin W. Raible, David W. |
author_sort | Stawicki, Tamara M. |
collection | PubMed |
description | Sensory hair cells are susceptible to numerous insults, including certain therapeutic medications like aminoglycoside antibiotics, and hearing and balance disorders are often a dose-limiting side effect of these medications. We show that mutations in multiple genes in both the retrograde intraflagellar transport (IFT) motor and adaptor complexes lead to resistance to aminoglycoside-induced hair cell death. These mutations also lead to defects in the entry of both aminoglycosides and the vital dye FM1-43 into hair cells, both processes that depend on hair cell mechanotransduction activity. However, the trafficking of proteins important for mechanotransduction activity is not altered by these mutations. Our data suggest that both retrograde IFT motor and adaptor complex genes are playing a role in aminoglycoside toxicity through affecting aminoglycoside uptake into hair cells. |
format | Online Article Text |
id | pubmed-6361216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63612162019-02-05 The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death Stawicki, Tamara M. Linbo, Tor Hernandez, Liana Parkinson, Lauren Bellefeuille, Danielle Rubel, Edwin W. Raible, David W. Biol Open Research Article Sensory hair cells are susceptible to numerous insults, including certain therapeutic medications like aminoglycoside antibiotics, and hearing and balance disorders are often a dose-limiting side effect of these medications. We show that mutations in multiple genes in both the retrograde intraflagellar transport (IFT) motor and adaptor complexes lead to resistance to aminoglycoside-induced hair cell death. These mutations also lead to defects in the entry of both aminoglycosides and the vital dye FM1-43 into hair cells, both processes that depend on hair cell mechanotransduction activity. However, the trafficking of proteins important for mechanotransduction activity is not altered by these mutations. Our data suggest that both retrograde IFT motor and adaptor complex genes are playing a role in aminoglycoside toxicity through affecting aminoglycoside uptake into hair cells. The Company of Biologists Ltd 2018-12-21 /pmc/articles/PMC6361216/ /pubmed/30578252 http://dx.doi.org/10.1242/bio.038745 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Stawicki, Tamara M. Linbo, Tor Hernandez, Liana Parkinson, Lauren Bellefeuille, Danielle Rubel, Edwin W. Raible, David W. The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title | The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title_full | The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title_fullStr | The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title_full_unstemmed | The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title_short | The role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
title_sort | role of retrograde intraflagellar transport genes in aminoglycoside-induced hair cell death |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361216/ https://www.ncbi.nlm.nih.gov/pubmed/30578252 http://dx.doi.org/10.1242/bio.038745 |
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