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, 2009 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-19417007
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Cadeias Pesadas de Miosina
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Surdez
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Células Ciliadas Auditivas Internas
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article