The DOI matches its Crossref record; 106 of the 106 references it cites were found in a registry or an index.
A Single Common Portal for Clathrin-mediated Endocytosis of Distinct Cargo Governed by Cargo-selective Adaptors
Open accessAbstract
Sorting of transmembrane cargo into clathrin-coated vesicles requires endocytic adaptors, yet RNA interference (RNAi)-mediated gene silencing of the AP-2 adaptor complex only disrupts internalization of a subset of clathrin-dependent cargo. This suggests alternate clathrin-associated sorting proteins participate in cargo capture at the cell surface, and a provocative recent proposal is that discrete endocytic cargo are sorted into compositionally and functionally distinct clathrin coats. We show here that the FXNPXY-type internalization signal within cytosolic domain of the LDL receptor is recognized redundantly by two phosphotyrosine-binding domain proteins, Dab2 and ARH; diminishing both proteins by RNAi leads to conspicuous LDL receptor accumulation at the cell surface. AP-2–dependent uptake of transferrin ensues relatively normally in the absence of Dab2 and ARH, clearly revealing delegation of sorting operations at the bud site. AP-2, Dab2, ARH, transferrin, and LDL receptors are all present within the vast majority of clathrin structures at the surface, challenging the general existence of specialized clathrin coats for segregated internalization of constitutively internalized cargo. However, Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss.
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In the citing paper
“LDL and transferrin initially enter into common endosomes via clathrin-mediated endocytosis but then quickly segregate[26–28].”
From Genome-scale CRISPR screening for modifiers of cellular LDL uptake (2021) · cites this paper as [26]
In the citing paper
“Similarly, knockdown of EPN1 in HeLa cells did not block internalization of LDL ( 4 ), supporting the idea that Epsin1 is not required for LDL or LDLR internalization.”
From The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation (2013) · cites this paper as [4]
In the citing paper
“Similarly, knockdown of EPN1 in HeLa cells did not block internalization of LDL ( 4 ), supporting the idea that Epsin1 is not required for LDL or LDLR internalization.”
From The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation (2013) · cites this paper as [4]
In the citing paper
“it appears to sort cargo into CCPs independently of AP2 (Garuti et al., 2005; Keyel et al., 2006; Maurer and Cooper, 2006).”
From Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis (2010) · cites this paper as Keyel et al., 2006
In the citing paper
“there are conflicting reports as to whether LDLR and TfnR are internalized via the same or distinct CCPs (Keyel et al., 2006; Lakadamyali et al., 2006).”
From Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis (2010) · cites this paper as Keyel et al., 2006
In the citing paper
“In agreement with previous studies (Morris and Cooper, 2001; Keyel et al., 2006; Maurer and Cooper, 2006; Chetrit et al., 2009), we observed colocalization of exogenously expressed mCherry-labeled Dab2 with clathrin-coat components in control cells.”
From Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis (2010) · cites this paper as Keyel et al., 2006
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Cited by
Sorted by citations
Molecular mechanism and physiological functions of clathrin-mediated endocytosis
McMahon, H. T., & Boucrot, E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3151 · Cited by 2,223
Endocytosis and signalling: intertwining molecular networks
Sorkin, A., & von Zastrow, M. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2748 · Cited by 1,064
Tickets to ride: selecting cargo for clathrin-regulated internalization
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Metadata
- Authors
- Keyel, P. A., Mishra, S. K., Roth, R., Heuser, J. E., Watkins, S. C., & Traub, L. M.
- Affiliations
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2006-10
- Volume
- 17
- Issue
- 10
- Pages
- 4300-4317
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W1970268623
- Semantic Scholar
- 354796a98c8bf83ff7cfbbb3a43519acb1b8febd
- Cited by
- 134
- References
- 106
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 15 · 2012: 15
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053249)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- clathrin-mediated endocytosis, AP-2, Dab2, ArH+, LDL receptor, transferrin uptake, phosphotyrosine binding domain, receptor sorting, hepatocytes, hypercholesterolemia, RNA interference
- MeSH terms
- Animals, Cells, Cultured, Clathrin, Coated Pits, Cell-Membrane, Endocytosis, Golgi Apparatus, HeLa Cells, Humans, Cholesterol, LDL, Receptors, LDL, Transfection, ras GTPase-Activating Proteins, Protein Transport, Clathrin-Coated Vesicles, Hepatocytes, Adaptor Protein Complex 2, RNA Interference, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Rats
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