Piezo1 links mechanical forces to red blood cell volume

Piezo1 links mechanical forces to red blood cell volume

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease x...

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Main Authors: Cahalan, Stuart M, Lukacs, Viktor, Ranade, Sanjeev S, Chien, Shu, Bandell, Michael, Patapoutian, Ardem
Format: Online
Language:English
Published: eLife Sciences Publications, Ltd 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456639/
id pubmed-4456639
recordtype oai_dc
spelling pubmed-44566392015-06-05 Piezo1 links mechanical forces to red blood cell volume Cahalan, Stuart M Lukacs, Viktor Ranade, Sanjeev S Chien, Shu Bandell, Michael Patapoutian, Ardem Cell Biology Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis. eLife Sciences Publications, Ltd 2015-05-22 /pmc/articles/PMC4456639/ /pubmed/26001274 http://dx.doi.org/10.7554/eLife.07370 Text en © 2015, Cahalan et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Cahalan, Stuart M
Lukacs, Viktor
Ranade, Sanjeev S
Chien, Shu
Bandell, Michael
Patapoutian, Ardem
spellingShingle Cahalan, Stuart M
Lukacs, Viktor
Ranade, Sanjeev S
Chien, Shu
Bandell, Michael
Patapoutian, Ardem
Piezo1 links mechanical forces to red blood cell volume
author_facet Cahalan, Stuart M
Lukacs, Viktor
Ranade, Sanjeev S
Chien, Shu
Bandell, Michael
Patapoutian, Ardem
author_sort Cahalan, Stuart M
title Piezo1 links mechanical forces to red blood cell volume
title_short Piezo1 links mechanical forces to red blood cell volume
title_full Piezo1 links mechanical forces to red blood cell volume
title_fullStr Piezo1 links mechanical forces to red blood cell volume
title_full_unstemmed Piezo1 links mechanical forces to red blood cell volume
title_sort piezo1 links mechanical forces to red blood cell volume
description Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.
publisher eLife Sciences Publications, Ltd
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456639/
_version_ 1613232081838538752

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