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

Authors :
Bartolomé A
Liang J
Wang P
Ho DD
Pajvani UB
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2020 Sep 01. Date of Electronic Publication: 2020 Sep 01.
Publication Year :
2020

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.

Details

Language :
English
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
32908985
Full Text :
https://doi.org/10.1101/2020.09.01.277954