ArticleNature medicine2014
The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 99 citations in OpenAlex.
- Dual functions of NPC1L1 for cholesterol transport: Cholesterol capture and regulation of inner-leaflet cholesterol accessibility.iScience · 2026Article
- Surface-displayed cholesterol enhances penetration and anti-tumor activity of a platinum nanodrug by targeting NPC1L1-expressing cancer associated fibroblasts.Nature communications · 2026Article
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Ultrasound-Triggered NPC1L1-Targeting Nanobubbles for Remodeling the Tumor Microenvironment in Pancreatic Cancer Chemoimmunotherapy.ACS applied materials & interfaces · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- From Genetic Findings to new Intestinal Molecular Targets in Lipid Metabolism.Current atherosclerosis reports · 2025Review
- Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane.Gastroenterology report · 2025Review
- Inhibition of liver cholesterol synthesis by a diet-induced gut hormone.Acta pharmaceutica Sinica. B · 2024Article
- Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.Science (New York, N.Y.) · 2023Article
- Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling.Nature communications · 2023Article
- The TICE Pathway: Mechanisms and Potential Clinical Applications.Current atherosclerosis reports · 2023Review
- Intracellular Cholesterol Trafficking.Cold Spring Harbor perspectives in biology · 2023Review
- Fluorescent visualization and evaluation of NPC1L1-mediated vesicular endocytosis during intestinal cholesterol absorption in mice.Life metabolism · 2023Article
- Review
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Lowering low-density lipoprotein cholesterol: from mechanisms to therapies.Life metabolism · 2022Review
- Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy.EMBO molecular medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypercholesterolemia, typically due to excessive cholesterol uptake, is a major risk factor for cardiovascular disease, which is responsible for ∼50% of all deaths in developed societies. Although it has been shown that intestinal cholesterol absorption is mediated by vesicular endocytosis of the Niemann-Pick C1-like 1 (NPC1L1) protein, the mechanism of sterol-stimulated NPC1L1 internalization is still mysterious. Here, we identified an endocytic peptide signal, YVNXXF (where X stands for any amino acid), in the cytoplasmic C-terminal tail of NPC1L1. Cholesterol binding on the N-terminal domain of NPC1L1 released the YVNXXF-containing region of NPC1L1 from association with the plasma membrane and enabled Numb binding. We also found that Numb, a clathrin adaptor, specifically recognized this motif and recruited clathrin for internalization. Disrupting the NPC1L1-Numb interaction decreased cholesterol uptake. Ablation of Numb in mouse intestine significantly reduced dietary cholesterol absorption and plasma cholesterol level. Together, these data show that Numb is a pivotal protein for intestinal cholesterol absorption and may provide a therapeutic target for hypercholesterolemia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.