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

Scientific Reports
Alberto BartoloméUtpal B Pajvani


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.


May 10, 1996·The Journal of Biological Chemistry·J ArribasJ Massagué
Jun 7, 2002·Genes & Development·Christy J FryerKatherine A Jones
Jun 3, 2004·Nature Reviews. Molecular Cell Biology·Raphael Kopan, Ma Xenia G Ilagan
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
Oct 13, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Ivana Ignjacev-LazichHaralambos Gavras
Dec 15, 2006·Nature·Ursula DanilczykJosef M Penninger
Apr 22, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sonja KowalczukStefan Bröer
May 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shiori HagaYukihito Ishizaka
May 21, 2009·European Journal of Clinical Investigation·G Y OuditJ Butany
Feb 22, 2011·Journal of Alzheimer's Disease : JAD·Annakaisa Haapasalo, Dora M Kovacs
May 21, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gael BarthetNikolaos K Robakis
Jun 26, 2013·Biochimica Et Biophysica Acta·Todd E GoldeLucio Miele
Dec 1, 2015·Trends in Immunology·Derk AmsenRonald A Backer
Dec 25, 2015·Proceedings of the National Academy of Sciences of the United States of America·David M BolducMichael S Wolfe
Sep 13, 2017·Molecular and Cellular Biology·Alberto BartoloméManuel Benito
May 16, 2018·G3 : Genes - Genomes - Genetics·Sarah EdieRoger H Reeves
Oct 31, 2018·The Journal of Clinical Investigation·Alberto BartolomeUtpal B Pajvani
Apr 11, 2020·Basic Research in Cardiology·Paola RizzoRoberto Ferrari
Apr 16, 2020·Circulation·Peter P LiuHongliang Li
Jul 23, 2020·European Journal of Clinical Pharmacology·Georgia Ragia, Vangelis G Manolopoulos

❮ Previous
Next ❯

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.