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Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography
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 c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776254/ https://www.ncbi.nlm.nih.gov/pubmed/34964715 http://dx.doi.org/10.7554/eLife.74512 |
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author | Elferich, Johannes Clark, Sarah Ge, Jingpeng Goehring, April Matsui, Aya Gouaux, Eric |
author_facet | Elferich, Johannes Clark, Sarah Ge, Jingpeng Goehring, April Matsui, Aya Gouaux, Eric |
author_sort | Elferich, Johannes |
collection | PubMed |
description | 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 other filamentous proteins, perhaps including CDH23. The PCDH15 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 PCDH15 complexes and, by extension, might include multiple MT complexes. |
format | Online Article Text |
id | pubmed-8776254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-87762542022-01-21 Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography Elferich, Johannes Clark, Sarah Ge, Jingpeng Goehring, April Matsui, Aya Gouaux, Eric eLife Neuroscience 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 other filamentous proteins, perhaps including CDH23. The PCDH15 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 PCDH15 complexes and, by extension, might include multiple MT complexes. eLife Sciences Publications, Ltd 2021-12-29 /pmc/articles/PMC8776254/ /pubmed/34964715 http://dx.doi.org/10.7554/eLife.74512 Text en © 2021, Elferich et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Elferich, Johannes Clark, Sarah Ge, Jingpeng Goehring, April Matsui, Aya Gouaux, Eric Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title | Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title_full | Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title_fullStr | Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title_full_unstemmed | Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title_short | Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
title_sort | molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776254/ https://www.ncbi.nlm.nih.gov/pubmed/34964715 http://dx.doi.org/10.7554/eLife.74512 |
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