Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex.
Sci Rep
; 11(1): 9803, 2021 05 07.
Article
in English
| MEDLINE | ID: covidwho-1262011
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
/
Amyloid Precursor Protein Secretases
/
Presenilin-1
/
Presenilin-2
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Rep
Year:
2021
Document Type:
Article
Affiliation country:
S41598-021-89379-x
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