Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell
Copyright policy )Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell
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.
- Institut für Humangenetik Germany
- University of Tübingen Germany
- University of Sheffield United Kingdom
Hair Cells, Auditory, Inner, Myosin Heavy Chains, Molecular Sequence Data, Membrane Proteins, Mice, Transgenic, Deafness, Exocytosis, Disease Models, Animal, Mice, Protein Transport, Two-Hybrid System Techniques, Synapses, Animals, Humans, Calcium, Amino Acid Sequence, Protein Binding
Hair Cells, Auditory, Inner, Myosin Heavy Chains, Molecular Sequence Data, Membrane Proteins, Mice, Transgenic, Deafness, Exocytosis, Disease Models, Animal, Mice, Protein Transport, Two-Hybrid System Techniques, Synapses, Animals, Humans, Calcium, Amino Acid Sequence, Protein Binding
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