Involvement of cochlin binding to sulfated heparan sulfate/heparin in the pathophysiology of autosomal dominant late-onset hearing loss (DFNA9).

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

SUBMITTER: Honda T 

PROVIDER: S-EPMC9333281 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature