UMass Chan Medical School Faculty Publications
UMMS Affiliation
RNA Therapeutics Institute
Publication Date
2021-10-01
Document Type
Article Preprint
Disciplines
Biochemistry, Biophysics, and Structural Biology | Musculoskeletal, Neural, and Ocular Physiology | Neuroscience and Neurobiology
Abstract
Mechanosensory transduction (MT), the conversion of mechanical stimuli into electrical signals, underpins hearing and balance and is carried out within hair cells in the inner ear. Hair cells harbor actin-filled stereocilia, arranged in rows of descending heights, where the tips of stereocilia are connected to their taller neighbors by a filament composed of protocadherin 15 (PCDH15) and cadherin 23 (CDH23), deemed the ‘tip-link’. Tension exerted on the tip-link opens an ion channel at the tip of the shorter stereocilia, thus converting mechanical force into an electrical signal. While biochemical and structural studies have provided insights into the molecular composition and structure of isolated portions of the tip-link, the architecture, location and conformational states of intact tip-links, on stereocilia, remains unknown. Here we report in situ cryo-electron microscopy imaging of the tip-link in mouse stereocilia. We observe individual PCDH15 molecules at the tip and shaft of stereocilia and determine their stoichiometry, conformational heterogeneity, and their complexes with CDH23. The PCDH15/CDH23 complexes occur in clusters, frequently with more than one copy of PCDH15 at the tip of stereocilia, suggesting that tip-links might consist of more than one copy of the PCDH15/CDH23 heterotetramer and by extension, might include multiple MT complexes.
Keywords
Neuroscience, Mechanosensory transduction, stereocilia
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2021.10.01.462800
Source
bioRxiv 2021.10.01.462800; doi: https://doi.org/10.1101/2021.10.01.462800. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
J, Clark S, Ge J, Oregon Health & Science University, Matsui A, Gouaux E. (2021). Molecular structure and conformation of stereocilia tip-links elucidated by cryo-electron tomography [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.10.01.462800. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2092
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Neuroscience and Neurobiology Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.