![]() ![]() Three clinical subtypes are distinguished on the basis of differences in the severity of hearing impairment and the presence of vestibular dysfunction, whereas progressive visual loss due to retinitis pigmentosa with variable age of onset occurs in all three USH types. Usher syndrome (USH) is the most frequent cause of hereditary deaf–blindness in humans. the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles. Our results strongly suggest that congenital deafness in USH type I and type II shares similar pathogenic mechanisms, i.e. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. By co-immunoprecipitation and in vitro binding assays, we establish that the usherin cytodomain can bind to whirlin and harmonin, two PDZ domain-containing proteins that are defective in genetic forms of isolated deafness and USH type I, respectively. Several lines of evidence support the involvement of TM usherin in the composition of the ankle links, a subset of filamentous lateral links connecting stereocilia at the base. The usherin immunolabeling is transient in the hair bundles of cochlear hair cells (HCs), but persists in mature hair bundles of vestibular HCs. In mouse and rat inner ears, we show that TM usherin is present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. In addition, we identified in the usherin cytoplasmic region a predicted 24 amino acid peptide, derived from a newly defined exon that is predominantly expressed in the inner ear but not in the retina. Analysis of the usherin alternative transcripts in the murine inner ear revealed the existence of several predicted TM usherin isoforms with modular ectodomains of different lengths. Here, we address the role of TM usherin in the inner ear. A much larger USH2A transcript predicted to encode a transmembrane (TM) isoform was recently reported. USH2A encodes usherin, which was previously defined as a basement membrane protein. It is the most common genetic form of USH. Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing impairment and retinitis pigmentosa. ![]()
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