Endocytosis via galactose receptors in vivo

Schlepper-Schäfer, Jutta; Hülsmann, D.; Djovkar, Assadollah; Meyer, Helmut E.; Herbertz, L; Kolb, Hubert; Kolb-Bachofen, Victoria

doi:10.1016/0014-4827(86)90602-6

Cited by 69 publications

(31 citation statements)

References 30 publications

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“…The hepatic ASGPR can bind and initiate the phagocytosis of particles less than 8 nm in diameter (43). Large particles such as platelets could be bound and processed by the macrophage ASGPR, which differs in molecular weight, membrane anchorage, and receptor arrangement (43,44).…”

Section: Discussionmentioning

confidence: 99%

Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands

Ellies

Ditto

Lévy

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

172

184

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A number of poorly characterized genetic modifiers contribute to the extensive variability of von Willebrand disease, the most prevalent bleeding disorder in humans. We find that a genetic lesion inactivating the murine ST3Gal-IV sialyltransferase causes a bleeding disorder associated with an autosomal dominant reduction in plasma von Willebrand factor (VWF) and an autosomal recessive thrombocytopenia. Although both ST3Gal-IV and ST6Gal-I sialyltransferases mask galactose linkages implicated as asialoglycoprotein receptor ligands, only ST3Gal-IV deficiency promotes asialoglycoprotein clearance mechanisms with a reduction in plasma levels of VWF and platelets. Exposed galactose on VWF was also found in a subpopulation of humans with abnormally low VWF levels. Oligosaccharide branch-specific sialylation by the ST3Gal-IV sialyltransferase is required to sustain the physiologic half-life of murine hemostatic components and may be an important modifier of plasma VWF level in humans.

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Section: Discussionmentioning

confidence: 99%

Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands

Ellies

Ditto

Lévy

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

172

184

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“…There are several reports of a characteristic ligand size limitation for the ASGP receptor (36 -39, 49). Using lactosylated bovine serum albumin conjugated to gold particles of various sizes, Schlepper-Schä fer et al (36) found that the cut-off size for the internalization of ligands of different sizes by liver hepatocytes was 8 nm in diameter (size of gold particles counted inside hepatocytes in EM photographs of histological sections of the liver after injection of ligand). However, the actual size may be larger since the conjugation of lactosylated bovine serum albumin to the gold particle may had changed the size and state of aggregation of the particle.…”

Section: Figmentioning

confidence: 99%

Biochemical and Functional Characterization of DNA Complexes Capable of Targeting Genes to Hepatocytes via the Asialoglycoprotein Receptor

Perales¹,

Grossmann²,

Molas³

et al. 1997

Journal of Biological Chemistry

122

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Functional genes can be introduced into mammalian cells in vitro by a variety of physical methods, including direct microinjection, electroporation, and co-precipitation with calcium phosphate. Most of these techniques, however, are impractical for delivering genes into tissues of intact animals. In contrast, receptor-mediated gene transfer has been shown to successfully introduce DNA into suitable recipient cells, both in vitro and in vivo (1-12). This procedure involves the formation of a complex between DNA and a polycation (such as poly-L-lysine), which bears a covalently linked ligand moiety specific for a given receptor on the surface of cells in the target tissue. The gene is internalized by the tissue, transported to the nucleus, and expressed in the cell for varying lengths of time (1,3,6,11). The overall level of expression of the transgene in the target tissue is dependent on several factors, such as the stability of the DNA/ligand⅐poly-L-lysine complex, the presence and number of specific receptors on the surface of the targeted cell, the receptor-DNA/ligand interaction, endocytosis of the DNA complex and the efficiency of gene transcription in the nucleus of the target cells.DNA in the nucleus of a higher eukaryote is intimately associated with basic nuclear proteins rich in lysine (i.e. histones) or arginine (i.e. protamines). The interaction of DNA with these basic proteins is responsible for the control of the condensation process that occurs upon chromosome formation during metaphase and is thought to play a role in the regulation of gene expression. DNA condensation, which occurs naturally in viruses, bacteria, and eukaryote nuclei, has been extremely difficult to reproduce in the laboratory (13,14). Due to the high negative charge of the DNA phosphate backbone, an increase in the degree of charge neutralization of the DNA theoretically results in extensive condensation and the separation of the DNA phase in the form of insoluble compact structures (15, 16). We have found, however, that the structure and stoichiometry of DNA⅐polycation complexes in solution can be manipulated by means of the process by which DNA⅐cationic polypeptide complexes are formed.Specific complexes of DNA (⌿-DNA) are formed with cationic homo-polypeptides (poly-L-lysine, poly-L-arginine, or poly-L-ornithine) after "annealing" both components in a step-down dialysis from NaCl concentrations of 3 to 0.010 M (11, 16). In contrast, direct addition of basic polypeptides to DNA at physiological salt concentrations results in reversible molecular aggregation and the formation of precipitates (7,17,18). Shapiro et al. (16) elucidated changes in DNA secondary structure in DNA⅐poly-L-lysine complexes prepared by directly mixing poly-L-lysine and DNA. The physical properties of the resulting soluble complexes were investigated by circular dichroism (CD) and optical rotatory dispersion. A change in the magnitude of the molar residue rotation was found, with a characteristic red shift and a strong negative rotatory transition center...

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“…Optimal recognition by the receptor was attained for tetra-and tri-antennary galactosides in which the separate galactose units are spaced at least 1.5 nm [6]; the affinity decreased significantly with decreasing glycose valency of the cluster glycoside [4]. Previous studies have demonstrated that, in vivo, the asialoglycoprotein receptor is responsible for uptake of small galactose-exposing particles [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Electron-microscopic studies using gold particles coated with asialofetuin or lactosylated BSA have revealed that the galactose-particle receptor is an oligomeric membraneassociated protein. After binding to this receptor, galactoseexposing particles are internalized and subsequently processed via a lysosomal pathway [8,[12][13][14]. Schlepper-Schafer et al [8] observed that the galactose-particle receptor accounted for the preferential uptake of galactose-exposing particles larger than 7.8 nm.…”

Section: Introductionmentioning

confidence: 99%

“…After binding to this receptor, galactoseexposing particles are internalized and subsequently processed via a lysosomal pathway [8,[12][13][14]. Schlepper-Schafer et al [8] observed that the galactose-particle receptor accounted for the preferential uptake of galactose-exposing particles larger than 7.8 nm. Studies of Bijsterbosch and Van Berkel [9] and Bijsterbosch et al [15] were in agreement with these data, in as much as internalize these ligands, but from the high affinity of large ligands for the galactose-particle receptor and the strategic anatomical localization of the Kupffer cells in the liver.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ligand size is a major determinant of high-affinity binding of fucose- and galactose-exposing (lipo)proteins by the hepatic fucose receptor

Biessen

Bakkeren

Beuting

et al. 1994

Biochemical Journal

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Previous in vivo studies have demonstrated that small galactoseexposing particles are preferentially internalized by the asialoglycoprotein receptor on the parenchymal liver cell and large particles by the galactose-particle receptor on the Kupffer cell. In this study, we have investigated using in vitro binding studies whether the affinity for either receptor is affected by the ligand size. The asialoglycoprotein receptor appeared to bind and process lactosylated proteins irrespective oftheir size. In contrast, recognition of galactose-exposing proteins by the galactoseparticle receptor on the Kupffer cell was strongly dependent on size. The affinity increased 3000-fold with protein sizes increasing from 5 to 15 nm, reaching its maximum at approx. 1 nM for ligands larger than 15 nm. Apparently, the preferential in vivo uptake of large galactose-exposing ligands by Kupffer cells does not result from an inability of the parenchymal liver cells to

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Endocytosis via galactose receptors in vivo

Cited by 69 publications

References 30 publications

Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands

Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands

Biochemical and Functional Characterization of DNA Complexes Capable of Targeting Genes to Hepatocytes via the Asialoglycoprotein Receptor

Ligand size is a major determinant of high-affinity binding of fucose- and galactose-exposing (lipo)proteins by the hepatic fucose receptor

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