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Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability
AIMS: Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs), a key component of the endosomal sorting complex required for transport (ESCRT), has been implicated in many essential biological processes. However, the physiological role of endogenous Hgs in the vascular system has not prev...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820882/ https://www.ncbi.nlm.nih.gov/pubmed/32044971 http://dx.doi.org/10.1093/cvr/cvaa016 |
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author | Yu, Zhenyang Zeng, Jian Wang, Jun Cui, Yaxiong Song, Xiaopeng Zhang, Yizhe Cheng, Xuan Hou, Ning Teng, Yan Lan, Yu Chen, Yeguang Yang, Xiao |
author_facet | Yu, Zhenyang Zeng, Jian Wang, Jun Cui, Yaxiong Song, Xiaopeng Zhang, Yizhe Cheng, Xuan Hou, Ning Teng, Yan Lan, Yu Chen, Yeguang Yang, Xiao |
author_sort | Yu, Zhenyang |
collection | PubMed |
description | AIMS: Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs), a key component of the endosomal sorting complex required for transport (ESCRT), has been implicated in many essential biological processes. However, the physiological role of endogenous Hgs in the vascular system has not previously been explored. Here, we have generated brain endothelial cell (EC) specific Hgs knockout mice to uncover the function of Hgs in EC polarity and cerebrovascular stability. METHODS AND RESULTS: Knockout of Hgs in brain ECs led to impaired endothelial apicobasal polarity and brain vessel collapse in mice. We determined that Hgs is essential for recycling of vascular endothelial (VE)-cadherin to the plasma membrane, since loss of Hgs blocked trafficking of endocytosed VE-cadherin from early endosomes to recycling endosomes, and impaired the motility of recycling endosomes. Supportively, overexpression of the motor kinesin family member 13A (KIF13A) restored endosomal recycling and rescued abrogated polarized trafficking and distribution of VE-cadherin in Hgs knockdown ECs. CONCLUSION: These data uncover a novel physiological function of Hgs and support an essential role for the ESCRT machinery in the maintenance of EC polarity and cerebrovascular stability. |
format | Online Article Text |
id | pubmed-7820882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-78208822021-01-27 Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability Yu, Zhenyang Zeng, Jian Wang, Jun Cui, Yaxiong Song, Xiaopeng Zhang, Yizhe Cheng, Xuan Hou, Ning Teng, Yan Lan, Yu Chen, Yeguang Yang, Xiao Cardiovasc Res Original Articles AIMS: Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs), a key component of the endosomal sorting complex required for transport (ESCRT), has been implicated in many essential biological processes. However, the physiological role of endogenous Hgs in the vascular system has not previously been explored. Here, we have generated brain endothelial cell (EC) specific Hgs knockout mice to uncover the function of Hgs in EC polarity and cerebrovascular stability. METHODS AND RESULTS: Knockout of Hgs in brain ECs led to impaired endothelial apicobasal polarity and brain vessel collapse in mice. We determined that Hgs is essential for recycling of vascular endothelial (VE)-cadherin to the plasma membrane, since loss of Hgs blocked trafficking of endocytosed VE-cadherin from early endosomes to recycling endosomes, and impaired the motility of recycling endosomes. Supportively, overexpression of the motor kinesin family member 13A (KIF13A) restored endosomal recycling and rescued abrogated polarized trafficking and distribution of VE-cadherin in Hgs knockdown ECs. CONCLUSION: These data uncover a novel physiological function of Hgs and support an essential role for the ESCRT machinery in the maintenance of EC polarity and cerebrovascular stability. Oxford University Press 2020-02-11 /pmc/articles/PMC7820882/ /pubmed/32044971 http://dx.doi.org/10.1093/cvr/cvaa016 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles Yu, Zhenyang Zeng, Jian Wang, Jun Cui, Yaxiong Song, Xiaopeng Zhang, Yizhe Cheng, Xuan Hou, Ning Teng, Yan Lan, Yu Chen, Yeguang Yang, Xiao Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title | Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title_full | Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title_fullStr | Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title_full_unstemmed | Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title_short | Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
title_sort | hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820882/ https://www.ncbi.nlm.nih.gov/pubmed/32044971 http://dx.doi.org/10.1093/cvr/cvaa016 |
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