title: Myosin-1c interacts with hair-cell receptors through its calmodulin-binding IQ domains.
abstract: Myosin-1c plays an essential role in adaptation of hair-cell mechanoelectrical transduction. To mediate adaptation, myosin-1c must interact directly or indirectly with other components of the transduction apparatus, including the mechanically gated transduction channel. As a first step toward identifying myosin-1c receptors, we used recombinant myosin-1c fragments to identify specific binding sites in hair cells and to biochemically characterize their interaction with myosin-1c. Myosin-1c fragments bound to tips of hair-cell stereocilia, the location of transduction and adaptation. Surprisingly, this interaction did not depend on the C-terminal tail of myosin-1c, proposed previously to be the receptor-binding site of the molecule. Instead, the interaction of myosin-1c with stereociliary receptors depended on its calmodulin-binding IQ domains. This interaction was blocked by calmodulin, which probably bound to a previously unoccupied IQ domain of myosin-1c. The calcium-sensitive binding of calmodulin to myosin-1c may therefore modulate the interaction of the adaptation motor with other components of the transduction apparatus.
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Cyr
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Dumont
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gillespie
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D016367:Baculoviridae; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006309:Hearing / Q000502:physiology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D024461:Myosin Type I / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D011892:Rana catesbeiana; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D014981:Xenopus
chemical_list: D002147:Calmodulin; D008024:Ligands; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D024461:Myosin Type I; D002118:Calcium