| RRC ID |
72242
|
| 著者 |
Honda T, Kawasaki N, Yanagihara R, Tamura R, Murakami K, Ichimiya T, Matsumoto N, Nishihara S, Yamamoto K.
|
| タイトル |
Involvement of cochlin binding to sulfated heparan sulfate/heparin in the pathophysiology of autosomal dominant late-onset hearing loss (DFNA9).
|
| ジャーナル |
PLoS One
|
| Abstract |
Late-onset non-syndromic autosomal dominant hearing loss 9 (DFNA9) is a hearing impairment caused by mutations in the coagulation factor C homology gene (COCH). COCH encodes for cochlin, a major component of the cochlear extracellular matrix. Though biochemical and genetic studies have characterized the properties of wild-type and mutated cochlins derived from DFNA9, little is known about the underlying pathogenic mechanism. In this study, we established a cochlin reporter cell, which allowed us to monitor the interaction of cochlin with its ligand(s) by means of a β-galactosidase assay. We found a class of highly sulfated glycosaminoglycans (GAGs), heparin, that were selectively bound to cochlin. The interaction was distinctly abrogated by N-desulfation, but not by 2-O- or 6-O-desulfation. The binding of cochlin to GAG was diminished by all of the point mutations found in DFNA9 patients. Through GAG composition analysis and immunostaining using mouse cochlin/immunoglobulin-Fc fusion protein, we identified moderately sulfated GAGs in mouse cochlea tissue; this implies that cochlin binds to such sulfated GAGs in the cochlea. Since GAGs play an important role in cell growth and survival as co-receptors of signal transduction mechanisms, the interaction of cochlin with GAGs in the extracellular matrix could aid the pathological research of autosomal dominant late-onset hearing loss in DFNA9.
|
| 巻・号 |
17(7)
|
| ページ |
e0268485
|
| 公開日 |
2022-1-1
|
| DOI |
10.1371/journal.pone.0268485
|
| PII |
PONE-D-22-02196
|
| PMID |
35901072
|
| PMC |
PMC9333281
|
| MeSH |
Animals
Arthrogryposis
Deafness* / genetics
Extracellular Matrix Proteins / metabolism
Hearing Loss* / genetics
Hearing Loss, Sensorineural* / genetics
Heparin
Heparitin Sulfate
Mice
Sulfates
|
| IF |
2.74
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
