| First Author | Heidrych P | Year | 2009 |
| Journal | Hum Mol Genet | Volume | 18 |
| Issue | 15 | Pages | 2779-90 |
| PubMed ID | 19417007 | Mgi Jnum | J:150214 |
| Mgi Id | MGI:3849924 | Doi | 10.1093/hmg/ddp213 |
| Citation | Heidrych P, et al. (2009) Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell. Hum Mol Genet 18(15):2779-90 |
| abstractText | Otoferlin has been proposed to be the Ca(2+) sensor in hair cell exocytosis, compensating for the classical synaptic fusion proteins synaptotagmin-1 and synaptotagmin-2. In the present study, yeast two-hybrid assays reveal myosin VI as a novel otoferlin binding partner. Co-immunoprecipitation assay and co-expression suggest an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of otoferlin mutants and myosin VI mutant mice indicates non-complementary and complementary roles of myosin VI and otoferlin for synaptic maturation: (i) IHCs from otoferlin mutant mice exhibited a decoupling of CtBP2/RIBEYE and Ca(V)1.3 and severe reduction of exocytosis. (ii) Myosin VI mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature. (iii) Otoferlin and myosin VI mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in otoferlin mutant IHCs indicated disturbed transport of endocytotic membranes and link the above morphological changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral IHC membrane. |
