Myosin XVA and Other Genes Essential for Stereocilia Morphogenesis

Deafness & Other Communication Disorders

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Abstract

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. This large exon alone encodes about 1,200 amino acids and is alternatively sliced. We recently demonstrated that isoforms of myosin XVA that include exon 2 are necesary for hearing (Nal et al., 2007).