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Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin

Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotyp...

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Autores principales: Pedicini, Lucia, Miteva, Katarina T., Hawley, Verity, Gaunt, Hannah J., Appleby, Hollie L., Cubbon, Richard M., Marszalek, Katarzyna, Kearney, Mark T., Beech, David J., McKeown, Lynn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953990/
https://www.ncbi.nlm.nih.gov/pubmed/29765077
http://dx.doi.org/10.1038/s41598-018-25853-3
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author Pedicini, Lucia
Miteva, Katarina T.
Hawley, Verity
Gaunt, Hannah J.
Appleby, Hollie L.
Cubbon, Richard M.
Marszalek, Katarzyna
Kearney, Mark T.
Beech, David J.
McKeown, Lynn
author_facet Pedicini, Lucia
Miteva, Katarina T.
Hawley, Verity
Gaunt, Hannah J.
Appleby, Hollie L.
Cubbon, Richard M.
Marszalek, Katarzyna
Kearney, Mark T.
Beech, David J.
McKeown, Lynn
author_sort Pedicini, Lucia
collection PubMed
description Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotypic actin-driven tunneling nanotubes (TNTs) which could be important for intercellular transfer of information in vascular physiology. Here we sought insight into the triggers for TNT formation. Wheat germ agglutinin, a C-type lectin and known label for TNTs, unexpectedly caused striking induction of TNTs. A succinylated derivative was by contrast inactive, suggesting mediation by a sialylated protein. Through siRNA-mediated knockdown we identified that this protein was likely to be CD31, an important sialylated membrane protein normally at endothelial cell junctions. We subsequently considered thrombin as a physiological inducer of endothelial TNTs because it reduces junctional contact. Thrombin reduced junctional contact, redistributed CD31 and induced TNTs, but its effect on TNTs was CD31-independent. Thrombin-induced TNTs nevertheless required PKCα, a known mediator of thrombin-dependent junctional remodelling, suggesting a necessity for junctional proteins in TNT formation. Indeed, TNT-inducing effects of wheat germ agglutinin and thrombin were both correlated with cortical actin rearrangement and similarly Ca(2+)-dependent, suggesting common underlying mechanisms. Once formed, Ca(2+) signalling along TNTs was observed.
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spelling pubmed-59539902018-05-21 Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin Pedicini, Lucia Miteva, Katarina T. Hawley, Verity Gaunt, Hannah J. Appleby, Hollie L. Cubbon, Richard M. Marszalek, Katarzyna Kearney, Mark T. Beech, David J. McKeown, Lynn Sci Rep Article Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotypic actin-driven tunneling nanotubes (TNTs) which could be important for intercellular transfer of information in vascular physiology. Here we sought insight into the triggers for TNT formation. Wheat germ agglutinin, a C-type lectin and known label for TNTs, unexpectedly caused striking induction of TNTs. A succinylated derivative was by contrast inactive, suggesting mediation by a sialylated protein. Through siRNA-mediated knockdown we identified that this protein was likely to be CD31, an important sialylated membrane protein normally at endothelial cell junctions. We subsequently considered thrombin as a physiological inducer of endothelial TNTs because it reduces junctional contact. Thrombin reduced junctional contact, redistributed CD31 and induced TNTs, but its effect on TNTs was CD31-independent. Thrombin-induced TNTs nevertheless required PKCα, a known mediator of thrombin-dependent junctional remodelling, suggesting a necessity for junctional proteins in TNT formation. Indeed, TNT-inducing effects of wheat germ agglutinin and thrombin were both correlated with cortical actin rearrangement and similarly Ca(2+)-dependent, suggesting common underlying mechanisms. Once formed, Ca(2+) signalling along TNTs was observed. Nature Publishing Group UK 2018-05-15 /pmc/articles/PMC5953990/ /pubmed/29765077 http://dx.doi.org/10.1038/s41598-018-25853-3 Text en © The Author(s) 2018 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
Pedicini, Lucia
Miteva, Katarina T.
Hawley, Verity
Gaunt, Hannah J.
Appleby, Hollie L.
Cubbon, Richard M.
Marszalek, Katarzyna
Kearney, Mark T.
Beech, David J.
McKeown, Lynn
Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title_full Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title_fullStr Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title_full_unstemmed Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title_short Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
title_sort homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953990/
https://www.ncbi.nlm.nih.gov/pubmed/29765077
http://dx.doi.org/10.1038/s41598-018-25853-3
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