The asialoglycoprotein receptor: a model for endocytic transport receptors

Spiess, Martin

doi:10.1021/bi00495a001

Cited by 442 publications

(298 citation statements)

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“…The ASGP receptor is a hepatic transport receptor responsible for the rapid clearance of galactosyl-terminal glycoproteins from the circulation (Ashwell and Harford, 1982;Spiess, 1990). The cytoplasmic domain of its major subunit H1 contains a tyrosine-based sorting signal for efficient endocytosis and basolateral sorting (Geffen et al, 1993;Fuhrer et al, 1994).…”

Section: In Vitro Formation Of Recycling Vesicles Is Dependent On Temmentioning

confidence: 99%

“…They receive material from the cell surface by endocytosis and from the exocytic pathway via the trans-Golgi network (TGN), and they distribute it further to late endosomes and back to the TGN and the plasma membrane. Transport receptors like the transferrin receptor, the low-density lipoprotein (LDL) receptor, and the asialoglycoprotein (ASGP) receptor cycle continuously between the plasma membrane and early endosomes (Spiess, 1990;Trowbridge et al, 1993). Receptor-positive early endosomes can be subdivided into sorting endosomes and recycling endosomes (or endocytic recycling compartment, ERC).…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Pagano

Crottet

Prescianotto-Baschong

et al. 2004

MBoC

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The involvement of clathrin and associated adaptor proteins in receptor recycling from endosomes back to the plasma membrane is controversial. We have used an in vitro assay to identify the molecular requirements for the formation of recycling vesicles. Cells expressing the asialoglycoprotein receptor H1, a typical recycling receptor, were surface biotinylated and then allowed to endocytose for 10 min. After stripping away surface-biotin, the cells were permeabilized and the cytosol washed away. In a temperature-, cytosol-, and nucleotide-dependent manner, the formation of sealed vesicles containing biotinylated H1 could be reconstituted. Vesicle formation was strongly inhibited upon immunodepletion of adaptor protein (AP)-1, but not of AP-2 or AP-3, from the cytosol, and was restored by readdition of purified AP-1. Vesicle formation was stimulated by supplemented clathrin, but inhibited by brefeldin A, consistent with the involvement of ARF1 and a brefeldin-sensitive guanine nucleotide exchange factor. The GTPase rab4, but not rab5, was required to generate endosome-derived vesicles. Depletion of rabaptin-5/rabex-5, a known interactor of both rab4 and ␥-adaptin, stimulated and addition of the purified protein strongly inhibited vesicle production. The results indicate that recycling is mediated by AP-1/clathrin-coated vesicles and regulated by rab4 and rabaptin-5/rabex-5. INTRODUCTIONEarly endosomes are a major sorting station for proteins and membranes in eukaryotic cells (Gruenberg, 2001;Maxfield and McGraw, 2004). They receive material from the cell surface by endocytosis and from the exocytic pathway via the trans-Golgi network (TGN), and they distribute it further to late endosomes and back to the TGN and the plasma membrane. Transport receptors like the transferrin receptor, the low-density lipoprotein (LDL) receptor, and the asialoglycoprotein (ASGP) receptor cycle continuously between the plasma membrane and early endosomes (Spiess, 1990;Trowbridge et al., 1993). Receptor-positive early endosomes can be subdivided into sorting endosomes and recycling endosomes (or endocytic recycling compartment, ERC). Primary endocytic vesicles fuse to sorting endosomes where ligands dissociate from their receptors because of a reduced internal pH. The receptors exit into tubular membranes that form recycling endosomes, whereas the ligands with the main fluid volume mature to late endosomes ("geometrybased sorting"; Maxfield and McGraw, 2004). There seem to be two main recycling pathways from early endosomes to the plasma membrane: a fast one directly from sorting endosomes and a slower one via recycling endosomes (Sheff et al., 1999;Hao and Maxfield, 2000;.The mechanisms to generate endosome-derived recycling vesicles are not clear, because there are seemingly contradictory findings. In general, formation of transport vesicles between organelles of the endocytic and secretory pathways requires cytosolic coat proteins to be recruited at the membrane of the donor compartment. Among the established coat complexes, clathr...

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Section: In Vitro Formation Of Recycling Vesicles Is Dependent On Temmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Pagano

Crottet

Prescianotto-Baschong

et al. 2004

MBoC

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“…13 Multivalency and the presence of Ca 2+ ions are prerequisites for proper recognition and binding of the ligands to the carbohydrate recognition domain of the receptor. 14,15 The binding affinity of ligands varies from micromolar to low-nanomolar and depends on the number and spatial orientation of the sugar moieties present.…”

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confidence: 99%

“…These findings are consistent with the short recycling time (10− 15 min) reported for the ASGPR. 13 To evaluate the impact of the mode of administration on in vivo uptake, radiolabeled siRNA−GalNAc conjugate 23 (SI section 6) was administered by IV and SC routes. Substantially higher levels of 23 were observed in liver with SC administration; details are summarized in SI section 7.…”

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confidence: 99%

Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing

et al. 2014

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Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytes in vitro and in vivo. The ligands derived from GalNAc are compatible with solid-phase oligonucleotide synthesis and deprotection conditions, with synthesis yields comparable to those of standard oligonucleotides. Subcutaneous (SC) administration of siRNA−GalNAc conjugates resulted in robust RNAi-mediated gene silencing in liver. Refinement of the siRNA chemistry achieved a 5-fold improvement in efficacy over the parent design in vivo with a median effective dose (ED 50 ) of 1 mg/kg following a single dose. This enabled the SC administration of siRNA−GalNAc conjugates at therapeutically relevant doses and, importantly, at dose volumes of ≤1 mL. Chronic weekly dosing resulted in sustained dose-dependent gene silencing for over 9 months with no adverse effects in rodents. The optimally chemically modified siRNA−GalNAc conjugates are hepatotropic and long-acting and have the potential to treat a wide range of diseases involving liver-expressed genes.

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“…1 The targeted receptor is a hetero-oligomer of glycoproteins integrated into the hepatocyte plasma membrane that participates in calcium-dependent removal of serum desialylated glycoproteins. [2][3][4] The subunit composition of asialoglycoprotein receptor (ASGPR), its cellular distribution, and function have been relatively well characterized for human and some other species. [1][2][3][4] In this laboratory, the woodchuck ASGPR (WcASGPR) was identified.…”

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Complement-mediated cytotoxicity and inhibition of ligand binding to hepatocytes by woodchuck hepatitis virus-induced autoantibodies to asialoglycoprotein receptor

1998

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Hepadnavirus invasion in woodchucks has been identified as a potent inducer of autoantibodies against asialoglycoprotein receptor (anti-ASGPR), a molecule essentially unique to hepatocytes that mediate clearance of desialylated serum proteins. We evaluated the possible pathogenetic importance of anti-ASGPR triggered by woodchuck hepatitis virus (WHV), using anti-ASGPR-reactive serum immunoglobulins (Igs) from five animals with different stages of WHV hepatitis or self-limited WHV infection and isolated woodchuck hepatocytes or HepG2 cells as targets. The results revealed that WHV-induced anti-ASGPR can specifically inhibit asialoglycoprotein recognition by both homologous and heterologous liver cells, as tested in an asialofetuin (ASFN)-binding radioassay. However, the extent of the interference significantly varied (from 85% inhibition to none) for anti-ASGPR with similar titer from different animals, indicating a high degree of heterogeneity in the ASGPR epitope specificity and in the potential biological effects of these autoantibodies. The WHVtriggered anti-ASGPR also induced complement-mediated hepatocytolysis in a microculture tetrazolium (MTT) assay, which ranged from 8.9% ؎ 0.3% to 33.6% ؎ 3.6% (mean ؎ SD) for different animals and target cell numbers. This cytopathic effect was strictly ASGPR-specific, complementdependent, and was not related to the anti-ASGPR ability to inhibit ligand-hepatocyte binding. Our findings indicate that among pathways by which anti-ASGPR autoimmunity could cause liver damage, hepadnavirus-induced anti-ASGPR might impair hepatocytes by both disrupting clearance of desialylated proteins and activation of the complement-mediated cytolysis. These cytopathic effects might contribute to the pathogenesis, aggravate severity, and prolong recovery from liver injury in viral hepatitis. (HEPA-TOLOGY 1998;27:1623-1631.)

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The asialoglycoprotein receptor: a model for endocytic transport receptors

Cited by 442 publications

References 124 publications

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing

Complement-mediated cytotoxicity and inhibition of ligand binding to hepatocytes by woodchuck hepatitis virus-induced autoantibodies to asialoglycoprotein receptor

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