Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

Abstract Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may...

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Autores principales:	Alberto Bartolomé, Jiani Liang, Pengfei Wang, David D. Ho, Utpal B. Pajvani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1aa72151492a40cfb224c6aefc913fef
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spelling	oai:doaj.org-article:1aa72151492a40cfb224c6aefc913fef2021-12-02T15:38:10ZAngiotensin converting enzyme 2 is a novel target of the γ-secretase complex10.1038/s41598-021-89379-x2045-2322https://doaj.org/article/1aa72151492a40cfb224c6aefc913fef2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89379-xhttps://doaj.org/toc/2045-2322Abstract Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.Alberto BartoloméJiani LiangPengfei WangDavid D. HoUtpal B. PajvaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alberto Bartolomé Jiani Liang Pengfei Wang David D. Ho Utpal B. Pajvani Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
description	Abstract Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.
format	article
author	Alberto Bartolomé Jiani Liang Pengfei Wang David D. Ho Utpal B. Pajvani
author_facet	Alberto Bartolomé Jiani Liang Pengfei Wang David D. Ho Utpal B. Pajvani
author_sort	Alberto Bartolomé
title	Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
title_short	Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
title_full	Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
title_fullStr	Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
title_full_unstemmed	Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
title_sort	angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1aa72151492a40cfb224c6aefc913fef
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Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

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