| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-09-09 |
| タイトル |
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タイトル |
A novel splice site mutation of myosin VI in mice leads to stereociliary fusion caused by disruption of actin networks in the apical region of inner ear hair cells |
| 言語 |
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言語 |
eng |
| DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0183477 |
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関連名称 |
10.1371/journal.pone.0183477 |
| 資源タイプ |
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資源 |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 著者 |
Seki, Yuta
Miyasaka, Yuki
Suzuki, Sari
Wada, Kenta
Yasuda, Shumpei P.
Matsuoka, Kunie
Ohshiba, Yasuhiro
Endo, Kentaro
Ishii, Rie
Shitara, Hiroshi
Kitajiri, Shin-ichiro
Nakagata, Naomi
Takebayashi, Hirohide
Kikkawa, Yoshiaki
|
| 信州大学研究者総覧へのリンク |
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|
氏名 |
Kitajiri, Shin-ichiro |
|
URL |
http://soar-rd.shinshu-u.ac.jp/profile/ja.jUTCupyC.html |
| 出版者 |
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出版者 |
PUBLIC LIBRARY SCIENCE |
| 引用 |
|
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内容記述 |
PLOS ONE.12(8):e0183477(2017) |
| 書誌情報 |
PLOS ONE
巻 12,
号 8,
p. e0183477,
発行日 2017-08-23
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| 抄録 |
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内容記述 |
An unconventional myosin encoded by the myosin VI gene (MYO6) contributes to hearing loss in humans. Homozygous mutations of MYO6 result in nonsyndromic profound congenital hearing loss, DFNB37. Kumamoto shaker/waltzer (ksv) mice harbor spontaneous mutations, and homozygous mutants exhibit congenital defects in balance and hearing caused by fusion of the stereocilia. We identified a Myo6(c.1381G>A) mutation that was found to be a p.E461K mutation leading to alternative splicing errors in Myo6 mRNA in ksv mutants. An analysis of the mRNA and protein expression in animals harboring this mutation suggested that most of the abnormal alternatively spliced isoforms of MYO6 are degraded in ksv mice. In the hair cells of ksv/ksv homozygotes, the MYO6 protein levels were significantly decreased in the cytoplasm, including in the cuticular plates. MYO6 and stereociliary taper-specific proteins were mislocalized along the entire length of the stereocilia of ksv/ksv mice, thus suggesting that MYO6 attached to taper-specific proteins at the stereociliary base. Histological analysis of the cochlear hair cells showed that the stereociliary fusion in the ksv/ksv mutants, developed through fusion between stereociliary bundles, raised cuticular plate membranes in the cochlear hair cells and resulted in incorporation of the bundles into the sheaths of the cuticular plates. Interestingly, the expression of the stereociliary rootlet-specific TRIO and F-actin binding protein (TRIOBP) was altered in ksv/ksv mice. The abnormal expression of TRIOBP suggested that the rootlets in the hair cells of ksv/ksv mice had excessive growth. Hence, these data indicated that decreased MYO6 levels in ksv/ksv mutants disrupt actin networks in the apical region of hair cells, thereby maintaining the normal structure of the cuticular plates and rootlets, and additionally provided a cellular basis for stereociliary fusion in Myo6 mutants. |
| 資源タイプ（コンテンツの種類） |
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| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1932-6203 |
| PubMed |
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識別子タイプ |
PMID |
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関連識別子 |
https://www.ncbi.nlm.nih.gov/pubmed/28832620 |
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関連名称 |
28832620 |
| 権利 |
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|
権利情報 |
© 2017 Seki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| 出版タイプ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| WoS |
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|
URL |
http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000408355800060 |
26293369_01.pdf (99.4 MB)
