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A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17
The angiotensin Converting Enzyme 2 (ACE2) receptor is a key component of the renin-angiotensin-aldesterone system (RAAS) that mediates numerous effects in the cardiovascular system. It is also the cellular point of contact for the coronavirus spike protein. Cleavage of the receptor is both importan...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364680/ https://www.ncbi.nlm.nih.gov/pubmed/34416436 http://dx.doi.org/10.1016/j.bbrc.2021.08.040 |
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author | Healy, Eamonn F. Lilic, Marko |
author_facet | Healy, Eamonn F. Lilic, Marko |
author_sort | Healy, Eamonn F. |
collection | PubMed |
description | The angiotensin Converting Enzyme 2 (ACE2) receptor is a key component of the renin-angiotensin-aldesterone system (RAAS) that mediates numerous effects in the cardiovascular system. It is also the cellular point of contact for the coronavirus spike protein. Cleavage of the receptor is both important to its physiological function as well as being necessary for cell entry by the virus. Shedding of ACE2 by the metalloprotease ADAM17 releases a catalytically active soluble form of ACE2, but cleavage by the serine protease TMPRSS2 is necessary for virion internalization. Complicating the issue is the observation that circulating ACE2 can also bind to the virus effectively blocking attachment to the membrane-bound receptor. This work investigates the possibility that the inflammatory response to coronavirus infection can abrogate shedding by ADAM17, thereby favoring cleavage by TMPRSS2 and thus cell entry by the virion. |
format | Online Article Text |
id | pubmed-8364680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83646802021-08-15 A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 Healy, Eamonn F. Lilic, Marko Biochem Biophys Res Commun Article The angiotensin Converting Enzyme 2 (ACE2) receptor is a key component of the renin-angiotensin-aldesterone system (RAAS) that mediates numerous effects in the cardiovascular system. It is also the cellular point of contact for the coronavirus spike protein. Cleavage of the receptor is both important to its physiological function as well as being necessary for cell entry by the virus. Shedding of ACE2 by the metalloprotease ADAM17 releases a catalytically active soluble form of ACE2, but cleavage by the serine protease TMPRSS2 is necessary for virion internalization. Complicating the issue is the observation that circulating ACE2 can also bind to the virus effectively blocking attachment to the membrane-bound receptor. This work investigates the possibility that the inflammatory response to coronavirus infection can abrogate shedding by ADAM17, thereby favoring cleavage by TMPRSS2 and thus cell entry by the virion. Elsevier Inc. 2021-10-08 2021-08-15 /pmc/articles/PMC8364680/ /pubmed/34416436 http://dx.doi.org/10.1016/j.bbrc.2021.08.040 Text en © 2021 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Healy, Eamonn F. Lilic, Marko A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title | A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title_full | A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title_fullStr | A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title_full_unstemmed | A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title_short | A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 |
title_sort | model for covid-19-induced dysregulation of ace2 shedding by adam17 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364680/ https://www.ncbi.nlm.nih.gov/pubmed/34416436 http://dx.doi.org/10.1016/j.bbrc.2021.08.040 |
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