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 Ca2+ 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 an...
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Published in | Human molecular genetics Vol. 18; no. 15; pp. 2779 - 2790 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.08.2009
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Otoferlin has been proposed to be the Ca2+ 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 CaV1.3 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 Ca2+ 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. |
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Bibliography: | These authors contributed equally to this work. ark:/67375/HXZ-01MS159D-K istex:B2C56F4D9DF8EE169A884CB640312E10CB3F3586 ArticleID:ddp213 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0964-6906 1460-2083 |
DOI: | 10.1093/hmg/ddp213 |