Opin vísindi

NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease

NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease


Title: NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease
Author: Bindesbøll, Christian
Aas, Aleksander
Ogmundsdottir, Margret H   orcid.org/0000-0003-2836-9988
Pankiv, Serhiy
Reine, Trine
Zoncu, Roberto   orcid.org/0000-0003-1611-1891
Simonsen, Anne   orcid.org/0000-0003-4711-7057
Date: 2020-03-11
Language: English
Scope: 4528
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Scientific Reports;10(1)
ISSN: 2045-2322
DOI: 10.1038/s41598-020-61352-0
Subject: NBEAL1; SREBP2; Cholesterol; Coronary artery disease; Kólesteról; Gen; Kransæðasjúkdómar
URI: https://hdl.handle.net/20.500.11815/2154

Show full item record

Citation:

Bindesbøll, C., Aas, A., Ogmundsdottir, M.H. et al. NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease. Scientific Reports 10, 4528 (2020). https://doi.org/10.1038/s41598-020-61352-0

Abstract:

Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease. Here, we identify the large and poorly characterized BEACH domain protein Neurobeachin-like (NBEAL) 1 as a Golgi- associated protein required for regulation of cholesterol metabolism. NBEAL1 is most abundantly expressed in arteries. Genetic variants in NBEAL1 are associated with decreased expression of NBEAL1 in arteries and increased risk of coronary artery disease in humans. We show that NBEAL1 regulates cholesterol metabolism by modulating LDLR expression in a mechanism involving interaction with SCAP and PAQR3 and subsequent SREBP2-processing. Thus, low expression of NBEAL1 may lead to increased risk of coronary artery disease by downregulation of LDLR levels.

Description:

Publisher's version (útgefin grein)

Rights:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Files in this item

This item appears in the following Collection(s)