Roles and Interactions of Usher 1 Proteins in the Outer Retina.

Usher syndrome (USH) describes a group of inherited blindness-deafness disorders, resulting from retinal degeneration and cochlear dysfunction (Usher, 1914). There are three subtypes of Usher syndrome, Usher syndrome type 1 is the most severe of the three. Seven Usher 1 genes have been mapped (Usher 1A-G), and all show the same clinical phenotype in humans. The most common form is Usher 1B, which accounts for at least 50% of Usher 1 cases (Astuto et al., 2000). Usher 1B is caused by mutations in the gene, MYO7A, which encodes an unconventional myosin, myosin VIIa (Weil et al., 1995). Usher 1C has been shown to be caused by defects in the gene, USH1C, which encodes harmonin, a scaffold protein with PDZ domains (Verpy et al., 2000; Bitner-Glindzicz et al., 2000). PDZ proteins, such as harmonin, form multiprotein complexes that are localized in specific subcellular domains, such as the microvilli of epithelial cells, synaptic terminals and the tight junctions (Sheng and Sala, 2001). Alternative splicing of the USH1C gene results in multiple harmonin isoforms, named a, b and c (Verpy et al., 2000). The short isoform a is the most abundant of the three and is present in most tissues. Both harmonin and myosin VIIa have been found in the stereocilia of the hair cells in the inner ear and the microvilli of other epithelial cells (Wolfrum et al., 98; Verpy et al., 2000; Boöda et al., 2002). Recent studies have shown that these two proteins interact to shape the stereocilia bundle in the inner ear (Boöda et al., 2002). [ABSTRACT FROM AUTHOR]