ArticleProceedings of the National Academy of Sciences of the United States of America2002
The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 174 citations in OpenAlex.
- Interview With Barbara Pearse and the Clathrin Family Tree.Traffic (Copenhagen, Denmark) · 2026Article
- Growth-rate analysis of clathrin assembly: inferring endocytic kinetics in living cells and tissues.Frontiers in molecular biosciences · 2026Review
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- S-Nitrosylation: Mechanistic Links between Nitric Oxide Signaling and Atherosclerosis.Current atherosclerosis reports · 2025Review
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Unveiling Familial Hypercholesterolemia-Review, Cardiovascular Complications, Lipid-Lowering Treatment and Its Efficacy.International journal of molecular sciences · 2024Review
- Genetic and molecular architecture of familial hypercholesterolemia.Journal of internal medicine · 2023Review
- Deletion of LDLRAP1 Induces Atherosclerotic Plaque Formation, Insulin Resistance, and Dysregulated Insulin Response in Adipose Tissue.The American journal of pathology · 2022Article
- Endocytosis in the context-dependent regulation of individual and collective cell properties.Nature reviews. Molecular cell biology · 2021Review
- Dynamic interplay between cell membrane tension and clathrin-mediated endocytosis.Biology of the cell · 2021Review
- Linton Mark Traub (1962-2020).The Journal of cell biology · 2021Article
- Novel function for AP-1B during cell migration.Molecular biology of the cell · 2020Article
- Endocytosis in the adaptation to cellular stress.Cell stress · 2020Review
- Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations.Cells · 2019Review
- Coatopathies: Genetic Disorders of Protein Coats.Annual review of cell and developmental biology · 2019Review
- Genetic Markers for Coronary Artery Disease.Medicina (Kaunas, Lithuania) · 2018Review
- Novel functions of CCM1 delimit the relationship of PTB/PH domains.Biochimica et biophysica acta. Proteins and proteomics · 2017Article
- Weak Molecular Interactions in Clathrin-Mediated Endocytosis.Frontiers in molecular biosciences · 2017Review
- Comparative analysis of adaptor-mediated clathrin assembly reveals general principles for adaptor clustering.Molecular biology of the cell · 2016Article
- Static Clathrin Assemblies at the Peripheral Vacuole-Plasma Membrane Interface of the Parasitic Protozoan Giardia lamblia.PLoS pathogens · 2016Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The low density lipoprotein (LDL) receptor plays a pivotal role in cholesterol metabolism. Inherited mutations that disturb the activity of the receptor lead to elevations in plasma cholesterol levels and early-onset coronary atherosclerosis. Defects in either the LDL receptor or apolipoprotein B, the proteinaceous component of LDL particles that binds the LDL receptor, elevate circulating LDL-cholesterol levels in an autosomal-dominant fashion, with heterozygotes displaying values between homozygous and normal individuals. Rarely, similar clinical phenotypes occur with a recessive pattern of inheritance, and several genetic lesions in the autosomal recessive hypercholesterolemia (ARH) gene on chromosome 1 have been mapped in this class of patients. ARH has an N-terminal phosphotyrosine-binding (PTB) domain evolutionarily related to that found in Disabled-2 and numb, two endocytic proteins. PTB domains bind to the consensus sequence FXNPXY, corresponding to the internalization motif of the LDL receptor. We show here that in addition to the FXNPXY sequence, ARH binds directly to soluble clathrin trimers and to clathrin adaptors by a mode involving the independently folded appendage domain of the beta subunit. At steady state, ARH colocalizes with endocytic proteins in HeLa cells, and the LDL receptor fluxes through peripheral ARH-positive sites before delivery to early endosomes. Because ARH also binds directly to phosphoinositides, which regulate clathrin bud assembly at the cell surface, our data suggest that in ARH patients, defective sorting adaptor function in hepatocytes leads to faulty LDL receptor traffic and hypercholesterolemia.
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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.