Mutations of myosin XVA in humans and mice cause profound congenital deafness. Myosins are actin based molecular motors that have a conserved head (motor) and neck (light chain binding motifs) and highly divergent tail domains. The MYO15A tail contains several domains which are candidates for protein interaction motifs. The identification of proteins that functionally interact with MYO15 may provide the best means of determining the role of MYO15A in the auditory system. In addition, interacting proteins are themselves likely to play crucial roles in hearing and would be strong candidates for proteins encoded by deafness loci. We are therefore using a yeast two hybrid system to identify proteins that interact with the myosin XVA. Genes that encode poteins that interact with myosin XVA from these two screens will be further examined for biological relevance. Whirlin is one such partner of myosin XVa and is necessary for stereocilia elongation and staircase formation (Belyantseva et al. 2005). This past year we identified mutations in families segregating DFNB3 deafness due to mutations in exon 2 of MYO15A (Nal et al., 2007). This large exon alone encodes about 1,200 amino acids. We recently demonstrated that the isoform of myosin XVA that includes exon 2 are necesary for hearing in humans (Nal et al., 2007).
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