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Piezo’s membrane footprint and its contribution to mechanosensitivity

Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion chann...

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Detalles Bibliográficos
Autores principales: Haselwandter, Christoph A, MacKinnon, Roderick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317911/
https://www.ncbi.nlm.nih.gov/pubmed/30480546
http://dx.doi.org/10.7554/eLife.41968
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author Haselwandter, Christoph A
MacKinnon, Roderick
author_facet Haselwandter, Christoph A
MacKinnon, Roderick
author_sort Haselwandter, Christoph A
collection PubMed
description Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion channel interacts energetically with the cell membrane. Through membrane mechanical calculations, we show that Piezo1 deforms the membrane shape outside the perimeter of the channel into a curved ‘membrane footprint’. This membrane footprint amplifies the sensitivity of Piezo1 to changes in membrane tension, rendering it exquisitely responsive. We assert that the shape of the Piezo channel is an elegant example of molecular form evolved to optimize a specific function, in this case tension sensitivity. Furthermore, the predicted influence of the membrane footprint on Piezo gating is consistent with the demonstrated importance of membrane-cytoskeletal attachments to Piezo gating.
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spelling pubmed-63179112019-01-09 Piezo’s membrane footprint and its contribution to mechanosensitivity Haselwandter, Christoph A MacKinnon, Roderick eLife Structural Biology and Molecular Biophysics Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion channel interacts energetically with the cell membrane. Through membrane mechanical calculations, we show that Piezo1 deforms the membrane shape outside the perimeter of the channel into a curved ‘membrane footprint’. This membrane footprint amplifies the sensitivity of Piezo1 to changes in membrane tension, rendering it exquisitely responsive. We assert that the shape of the Piezo channel is an elegant example of molecular form evolved to optimize a specific function, in this case tension sensitivity. Furthermore, the predicted influence of the membrane footprint on Piezo gating is consistent with the demonstrated importance of membrane-cytoskeletal attachments to Piezo gating. eLife Sciences Publications, Ltd 2018-11-27 /pmc/articles/PMC6317911/ /pubmed/30480546 http://dx.doi.org/10.7554/eLife.41968 Text en © 2018, Haselwandter and MacKinnon 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 Structural Biology and Molecular Biophysics
Haselwandter, Christoph A
MacKinnon, Roderick
Piezo’s membrane footprint and its contribution to mechanosensitivity
title Piezo’s membrane footprint and its contribution to mechanosensitivity
title_full Piezo’s membrane footprint and its contribution to mechanosensitivity
title_fullStr Piezo’s membrane footprint and its contribution to mechanosensitivity
title_full_unstemmed Piezo’s membrane footprint and its contribution to mechanosensitivity
title_short Piezo’s membrane footprint and its contribution to mechanosensitivity
title_sort piezo’s membrane footprint and its contribution to mechanosensitivity
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317911/
https://www.ncbi.nlm.nih.gov/pubmed/30480546
http://dx.doi.org/10.7554/eLife.41968
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