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Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane

Localized Ca(2+) influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of T...

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Autores principales: Baratchi, Sara, Knoerzer, Markus, Khoshmanesh, Khashayar, Mitchell, Arnan, McIntyre, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698423/
https://www.ncbi.nlm.nih.gov/pubmed/29162902
http://dx.doi.org/10.1038/s41598-017-16276-7
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author Baratchi, Sara
Knoerzer, Markus
Khoshmanesh, Khashayar
Mitchell, Arnan
McIntyre, Peter
author_facet Baratchi, Sara
Knoerzer, Markus
Khoshmanesh, Khashayar
Mitchell, Arnan
McIntyre, Peter
author_sort Baratchi, Sara
collection PubMed
description Localized Ca(2+) influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin. Using dual-color imaging, we found that TRPV4 and β-catenin reside in similar islands and can be found at both the basolateral and basal membranes. Following shear stress stimulation, TRPV4 molecules formed smaller clusters, with the majority residing outside of clusters. Further shear stress stimulation changed the molecular distribution of TRPV4 molecules, limiting them to the basal membrane. This redistribution and the smaller clusters resulted in the segregation of TRPV4 from β-catenin. Furthermore, TRPV4 trafficking was controlled by focal adhesion kinase and activation of the α5ß1 integrin. These highly differentiated spatial redistributions suggest that mechanotransduction of blood flow is controlled via a more complex hierarchy than previously thought.
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spelling pubmed-56984232017-11-29 Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane Baratchi, Sara Knoerzer, Markus Khoshmanesh, Khashayar Mitchell, Arnan McIntyre, Peter Sci Rep Article Localized Ca(2+) influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin. Using dual-color imaging, we found that TRPV4 and β-catenin reside in similar islands and can be found at both the basolateral and basal membranes. Following shear stress stimulation, TRPV4 molecules formed smaller clusters, with the majority residing outside of clusters. Further shear stress stimulation changed the molecular distribution of TRPV4 molecules, limiting them to the basal membrane. This redistribution and the smaller clusters resulted in the segregation of TRPV4 from β-catenin. Furthermore, TRPV4 trafficking was controlled by focal adhesion kinase and activation of the α5ß1 integrin. These highly differentiated spatial redistributions suggest that mechanotransduction of blood flow is controlled via a more complex hierarchy than previously thought. Nature Publishing Group UK 2017-11-21 /pmc/articles/PMC5698423/ /pubmed/29162902 http://dx.doi.org/10.1038/s41598-017-16276-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Baratchi, Sara
Knoerzer, Markus
Khoshmanesh, Khashayar
Mitchell, Arnan
McIntyre, Peter
Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title_full Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title_fullStr Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title_full_unstemmed Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title_short Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
title_sort shear stress regulates trpv4 channel clustering and translocation from adherens junctions to the basal membrane
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698423/
https://www.ncbi.nlm.nih.gov/pubmed/29162902
http://dx.doi.org/10.1038/s41598-017-16276-7
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