Journal
SCIENCE
Volume 360, Issue 6393, Pages 1087-1092Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao6575
Keywords
-
Categories
Funding
- MOST of China [2016YFA0500100]
- NNSF of China [31690102, 31430044, 81260041, 31771568, 31701030, 91754102, U1403221, 31600651]
- Xinjiang Key Research and Development Project [2016B03053]
- Science and Technology Support Project of Xinjiang [2017E0269]
- 111 Project of Ministry of Education of China [B16036]
- Natural Science Foundation of Hubei Province [2016CFA012]
Ask authors/readers for more resources
A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available