ArticleMolecular biology of the cell2013
Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- TAT-1, a phosphatidylserine flippase, affects molting and regulates membrane trafficking in the epidermis of Caenorhabditis elegans.Genetics · 2025Article
- Loss of the Na+/K+ cation pump CATP-1 suppresses nekl-associated molting defects.G3 (Bethesda, Md.) · 2024Article
- The Caenorhabditis elegans cuticle and precuticle: a model for studying dynamic apical extracellular matrices in vivo.Genetics · 2024Review
- CED-6/GULP and components of the clathrin-mediated endocytosis machinery act redundantly to correctly display CED-1 on the cell membrane in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2024Article
- Evolutionary plasticity in the requirement for force exerted by ligand endocytosis to activate C. elegans Notch proteins.Current biology : CB · 2022Article
- An unexpected role for the conserved ADAM-family metalloprotease ADM-2 in Caenorhabditis elegans molting.PLoS genetics · 2022Article
- Control of clathrin-mediated endocytosis by NIMA family kinases.PLoS genetics · 2020Article
- Endocytic Adaptors in Cardiovascular Disease.Frontiers in cell and developmental biology · 2020Review
- Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation.Circulation research · 2019Article
- Actin organization and endocytic trafficking are controlled by a network linking NIMA-related kinases to the CDC-42-SID-3/ACK1 pathway.PLoS genetics · 2018Article
- Molting inWorm · 2017Review
- Article
- Eps15 membrane-binding and -bending activity acts redundantly with Fcho1 during clathrin-mediated endocytosis.Molecular biology of the cell · 2016Article
- Epsin1 modulates synaptic vesicle retrieval capacity at CNS synapses.Scientific reports · 2016Article
- Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans.Scientific reports · 2016Article
- A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes.Molecular and cellular biology · 2016Article
- C. elegans NIMA-related kinases NEKL-2 and NEKL-3 are required for the completion of molting.Developmental biology · 2015Article
- C. elegans as a model for membrane traffic.WormBook : the online review of C. elegans biology · 2014Review
- Ubiquitin-dependent sorting in endocytosis.Cold Spring Harbor perspectives in biology · 2014Review
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6 authors.
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Abstract
Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR.
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