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Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4
Endothelial cell motility has fundamental role in vasculogenesis and angiogenesis during developmental or pathological processes. Tks4 is a scaffold protein known to organize the cytoskeleton of lamellipodia and podosomes, and thus modulating cell motility and invasion. In particular, Tks4 is requir...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779758/ https://www.ncbi.nlm.nih.gov/pubmed/31591456 http://dx.doi.org/10.1038/s41598-019-50915-5 |
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author | Mehes, Elod Barath, Monika Gulyas, Marton Bugyik, Edina Geiszt, Miklos Szoor, Arpad Lanyi, Arpad Czirok, Andras |
author_facet | Mehes, Elod Barath, Monika Gulyas, Marton Bugyik, Edina Geiszt, Miklos Szoor, Arpad Lanyi, Arpad Czirok, Andras |
author_sort | Mehes, Elod |
collection | PubMed |
description | Endothelial cell motility has fundamental role in vasculogenesis and angiogenesis during developmental or pathological processes. Tks4 is a scaffold protein known to organize the cytoskeleton of lamellipodia and podosomes, and thus modulating cell motility and invasion. In particular, Tks4 is required for the localization and activity of membrane type 1-matrix metalloproteinase, a key factor for extracellular matrix (ECM) cleavage during cell migration. While its role in transformed cells is well established, little is known about the function of Tks4 under physiological conditions. In this study we examined the impact of Tks4 gene silencing on the functional activity of primary human umbilical vein endothelial cells (HUVEC) and used time-lapse videomicrosopy and quantitative image analysis to characterize cell motility phenotypes in culture. We demonstrate that the absence of Tks4 in endothelial cells leads to impaired ECM cleavage and decreased motility within a 3-dimensional ECM environment. Furthermore, absence of Tks4 also decreases the ability of HUVEC cells to form multicellular sprouts, a key requirement for angiogenesis. To establish the involvement of Tks4 in vascular development in vivo, we show that loss of Tks4 leads sparser vasculature in the fetal chorion in the Tks4-deficient ‘nee’ mouse strain. |
format | Online Article Text |
id | pubmed-6779758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67797582019-10-16 Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 Mehes, Elod Barath, Monika Gulyas, Marton Bugyik, Edina Geiszt, Miklos Szoor, Arpad Lanyi, Arpad Czirok, Andras Sci Rep Article Endothelial cell motility has fundamental role in vasculogenesis and angiogenesis during developmental or pathological processes. Tks4 is a scaffold protein known to organize the cytoskeleton of lamellipodia and podosomes, and thus modulating cell motility and invasion. In particular, Tks4 is required for the localization and activity of membrane type 1-matrix metalloproteinase, a key factor for extracellular matrix (ECM) cleavage during cell migration. While its role in transformed cells is well established, little is known about the function of Tks4 under physiological conditions. In this study we examined the impact of Tks4 gene silencing on the functional activity of primary human umbilical vein endothelial cells (HUVEC) and used time-lapse videomicrosopy and quantitative image analysis to characterize cell motility phenotypes in culture. We demonstrate that the absence of Tks4 in endothelial cells leads to impaired ECM cleavage and decreased motility within a 3-dimensional ECM environment. Furthermore, absence of Tks4 also decreases the ability of HUVEC cells to form multicellular sprouts, a key requirement for angiogenesis. To establish the involvement of Tks4 in vascular development in vivo, we show that loss of Tks4 leads sparser vasculature in the fetal chorion in the Tks4-deficient ‘nee’ mouse strain. Nature Publishing Group UK 2019-10-07 /pmc/articles/PMC6779758/ /pubmed/31591456 http://dx.doi.org/10.1038/s41598-019-50915-5 Text en © The Author(s) 2019 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 Mehes, Elod Barath, Monika Gulyas, Marton Bugyik, Edina Geiszt, Miklos Szoor, Arpad Lanyi, Arpad Czirok, Andras Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title | Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title_full | Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title_fullStr | Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title_full_unstemmed | Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title_short | Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4 |
title_sort | enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein tks4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779758/ https://www.ncbi.nlm.nih.gov/pubmed/31591456 http://dx.doi.org/10.1038/s41598-019-50915-5 |
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