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dc.contributor.authorElferich, Johannes
dc.contributor.authorClark, Sarah
dc.contributor.authorGe, Jingpeng
dc.contributor.authorMatsui, Aya
dc.contributor.authorGouaux, Eric
dc.date2022-08-11T08:08:28.000
dc.date.accessioned2022-08-23T15:56:03Z
dc.date.available2022-08-23T15:56:03Z
dc.date.issued2021-10-01
dc.date.submitted2021-12-01
dc.identifier.citationbioRxiv 2021.10.01.462800; doi: https://doi.org/10.1101/2021.10.01.462800. <a href="https://doi.org/10.1101/2021.10.01.462800" target="_blank" title="view preprint in biorxiv">Link to preprint on bioRxiv.</a>
dc.identifier.doi10.1101/2021.10.01.462800
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29886
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p>
dc.description.abstractMechanosensory 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.
dc.language.isoen_US
dc.relationNow published in eLife doi: 10.7554/eLife.74512
dc.rightsThe 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.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectNeuroscience
dc.subjectMechanosensory transduction
dc.subjectstereocilia
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectMusculoskeletal, Neural, and Ocular Physiology
dc.subjectNeuroscience and Neurobiology
dc.titleMolecular structure and conformation of stereocilia tip-links elucidated by cryo-electron tomography [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3126&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2092
dc.identifier.contextkey26421034
refterms.dateFOA2022-08-23T15:56:03Z
html.description.abstract<p>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 <em>in situ</em> 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.</p>
dc.identifier.submissionpathfaculty_pubs/2092
dc.contributor.departmentRNA Therapeutics Institute


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Except where otherwise noted, this item's license is described as 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.