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Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells
Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295575/ https://www.ncbi.nlm.nih.gov/pubmed/32484440 http://dx.doi.org/10.7554/eLife.50684 |
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author | Caolo, Vincenza Debant, Marjolaine Endesh, Naima Futers, T Simon Lichtenstein, Laeticia Bartoli, Fiona Parsonage, Gregory Jones, Elizabeth AV Beech, David J |
author_facet | Caolo, Vincenza Debant, Marjolaine Endesh, Naima Futers, T Simon Lichtenstein, Laeticia Bartoli, Fiona Parsonage, Gregory Jones, Elizabeth AV Beech, David J |
author_sort | Caolo, Vincenza |
collection | PubMed |
description | Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca(2+)-regulated transmembrane sheddase that mediates S2 Notch1 cleavage. Consistent with this observation, we found Piezo1-dependent increase in the abundance of Notch1 intracellular domain (NICD) that depended on ADAM10 and the downstream S3 cleavage enzyme, γ-secretase. Conditional endothelial-specific disruption of Piezo1 in adult mice suppressed the expression of multiple Notch1 target genes in hepatic vasculature, suggesting constitutive functional importance in vivo. The data suggest that Piezo1 is a mechanism conferring force sensitivity on ADAM10 and Notch1 with downstream consequences for sustained activation of Notch1 target genes and potentially other processes. |
format | Online Article Text |
id | pubmed-7295575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72955752020-06-17 Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells Caolo, Vincenza Debant, Marjolaine Endesh, Naima Futers, T Simon Lichtenstein, Laeticia Bartoli, Fiona Parsonage, Gregory Jones, Elizabeth AV Beech, David J eLife Cell Biology Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca(2+)-regulated transmembrane sheddase that mediates S2 Notch1 cleavage. Consistent with this observation, we found Piezo1-dependent increase in the abundance of Notch1 intracellular domain (NICD) that depended on ADAM10 and the downstream S3 cleavage enzyme, γ-secretase. Conditional endothelial-specific disruption of Piezo1 in adult mice suppressed the expression of multiple Notch1 target genes in hepatic vasculature, suggesting constitutive functional importance in vivo. The data suggest that Piezo1 is a mechanism conferring force sensitivity on ADAM10 and Notch1 with downstream consequences for sustained activation of Notch1 target genes and potentially other processes. eLife Sciences Publications, Ltd 2020-06-02 /pmc/articles/PMC7295575/ /pubmed/32484440 http://dx.doi.org/10.7554/eLife.50684 Text en © 2020, Caolo et al http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Cell Biology Caolo, Vincenza Debant, Marjolaine Endesh, Naima Futers, T Simon Lichtenstein, Laeticia Bartoli, Fiona Parsonage, Gregory Jones, Elizabeth AV Beech, David J Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title | Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title_full | Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title_fullStr | Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title_full_unstemmed | Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title_short | Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells |
title_sort | shear stress activates adam10 sheddase to regulate notch1 via the piezo1 force sensor in endothelial cells |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295575/ https://www.ncbi.nlm.nih.gov/pubmed/32484440 http://dx.doi.org/10.7554/eLife.50684 |
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