Mutant alleles of mammalian myosin XVA cause profound congenital deafness DFNB3. In humans worldwide, mutations of MYO15A apepars to be a common mutated gene associated with nonsyndromic deafness. Myosins are actin-activated molecular motors that have a conserved head (motor) and neck (light chain binding motifs) and highly divergent tail domains. The MYO15A tail contains several motifs that are candidates for protein interaction motifs. To date, isoform 1 of myosin XVa is the largest of all reported vertebrate myosins. The N-terminus of myosin XVa is composed of 1,220 residues. We previously demonstrated that isoform 1 is necessary for hearing (Nal et al., 2007). As a collaboration with Drs. Sally Camper and Gregory Frolenkov, a mouse model has been developed that has a defective amino terminus which recapitulates the human phenotype (unpublished data). The identification of proteins that functionally interact with MYO15 may provide a 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 other deafness loci. We are therefore using a yeast two hybrid system and MS screens 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 and EPS8 are reported partners of the tail domain of myosin XVa and are necessary for stereocilia elongation and staircase formation (Belyantseva et al. 2005). As a collaboration with Dr. Sellers (NHLBI), we are characterizing the biophysical properties of myosin XVa.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute on Deafness and Other Communication Disorders
Zip Code
Faridi, Rabia; Rehman, Atteeq U; Morell, Robert J et al. (2016) Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome. Clin Genet :
Rehman, Atteeq U; Bird, Jonathan E; Faridi, Rabia et al. (2016) Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness. Hum Mutat 37:991-1003
Imtiaz, Ayesha; Maqsood, Azra; Rehman, Atteeq U et al. (2016) Recessive mutations of TMC1 associated with moderate to severe hearing loss. Neurogenetics 17:115-23
Rehman, A U; Friedman, T B; Griffith, A J (2016) Unresolved questions regarding human hereditary deafness. Oral Dis :
Naz, S; Imtiaz, A; Mujtaba, G et al. (2016) Genetic causes of moderate to severe hearing loss point to modifiers. Clin Genet :
Mujtaba, Ghulam; Schultz, Julie M; Imtiaz, Ayesha et al. (2015) A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss. J Med Genet 52:548-52
Drummond, Meghan C; Barzik, Melanie; Bird, Jonathan E et al. (2015) Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear. Nat Commun 6:6873
Morozko, Eva L; Nishio, Ayako; Ingham, Neil J et al. (2015) ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells. Hum Mol Genet 24:609-24
Fang, Qing; Indzhykulian, Artur A; Mustapha, Mirna et al. (2015) The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Elife 4:
Bird, Jonathan E; Takagi, Yasuharu; Billington, Neil et al. (2014) Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking. Proc Natl Acad Sci U S A 111:12390-5

Showing the most recent 10 out of 19 publications