Sci Rep . Angiotensin converting enzyme 2 is a novel target of the ?-secretase complex

[tetano]

Sci Rep


. 2021 May 7;11(1):9803.
doi: 10.1038/s41598-021-89379-x.
Angiotensin converting enzyme 2 is a novel target of the ?-secretase complex


Alberto Bartolom? ¹ , Jiani Liang ¹ , Pengfei Wang ² , David D Ho ² , Utpal B Pajvani ³



Affiliations

• PMID: 33963249
• DOI: 10.1038/s41598-021-89379-x

Free article

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 ?-secretase (?S) targets, we hypothesized that ACE2 may be affected by ?S proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by ?S, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of ?S results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of ?S does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.