Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction
Open Access
- 27 June 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (28), 11476-11481
- https://doi.org/10.1073/pnas.1104161108
Abstract
In the most accepted model for hair cell mechanotransduction, a cluster of myosin motors located at the stereocilia upper tip-link density (UTLD) keeps the tip-link under tension at rest. Both myosin VIIa (MYO7A) and myosin 1c have been implicated in mechanotransduction based on functional studies. However, localization studies are conflicting, leaving open the question of which myosin localizes at the UTLD and generates the tip-link resting tension. Using immunofluorescence, we now show that MYO7A and sans, a MYO7A-interacting protein, cluster at the UTLD. Analysis of the immunofluorescence intensity indicates that eight or more MYO7A molecules are present at each UTLD, consistent with a direct role for MYO7A in maintaining tip-link tension. MYO7A and sans localization at the UTLD is confirmed by transfection of hair cells with GFP-tagged constructs for these proteins. Cotransfection studies in a heterologous system show that MYO7A, sans, and the UTLD protein harmonin-b form a tripartite complex and that each protein is capable of interacting with one another independently. We propose that MYO7A, sans, and harmonin-b form the core components of the UTLD molecular complex. In this complex, MYO7A is likely the motor element that pulls on CDH23 to exert tension on the tip-link.This publication has 41 references indexed in Scilit:
- Regulation of Stereocilia Length by Myosin XVa and Whirlin Depends on the Actin-Regulatory Protein Eps8Current Biology, 2011
- Robust Mechanosensing and Tension Generation by Myosin VIJournal of Molecular Biology, 2011
- Mechanotransduction by Hair Cells: Models, Molecules, and MechanismsCell, 2009
- Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cellsPflügers Archiv - European Journal of Physiology, 2009
- The tail binds to the head–neck domain, inhibiting ATPase activity of myosin VIIAProceedings of the National Academy of Sciences of the United States of America, 2009
- Harmonin Mutations Cause Mechanotransduction Defects in Cochlear Hair CellsNeuron, 2009
- A FERM domain autoregulates Drosophila myosin 7a activityProceedings of the National Academy of Sciences of the United States of America, 2009
- Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filamentsNature, 2009
- Dynamic length regulation of sensory stereociliaSeminars in Cell & Developmental Biology, 2008
- Mechano-electrical Transduction: New Insights into Old IdeasThe Journal of Membrane Biology, 2006