Niemann-Pick C1-like 1 (NPC1L1) is a polytopic transmembrane protein that plays a critical role in cholesterol absorption. Ezetimibe, a hypocholesterolemic drug, has been reported to bind NPC1L1 and block cholesterol absorption. However, the molecular mechanism of NPC1L1-mediated cholesterol uptake and how ezetimibe inhibits this process are poorly defined. Here we find that cholesterol specifically promotes the internalization of NPC1L1 and that this process requires microfilaments and the clathrin/AP2 complex. Blocking NPC1L1 endocytosis dramatically decreases cholesterol internalization, indicating that NPC1L1 mediates cholesterol uptake via its vesicular endocytosis. Ezetimibe prevents NPC1L1 from incorporating into clathrin-coated vesicles and thus inhibits cholesterol uptake. Together, our data suggest a model wherein cholesterol is internalized into cells with NPC1L1 through clathrin/AP2-mediated endocytosis and ezetimibe inhibits cholesterol absorption by blocking the internalization of NPC1L1.
Pharmacology, Toxicology and Pharmaceutical Science
12
6%
Other
14
7%
Unknown
61
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 21. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 August 2022.
All research outputs
#2,300,888
of 34,518,147 outputs
Outputs from Cell Metabolism (Science Direct)
#1,708
of 3,809 outputs
Outputs of similar age
#6,328
of 139,537 outputs
Outputs of similar age from Cell Metabolism (Science Direct)
#4
of 30 outputs
Altmetric has tracked 34,518,147 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,809 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 75.9. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 139,537 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.
