asialoglycoproteins

Summary

Summary: Endogenous glycoproteins from which SIALIC ACID has been removed by the action of sialidases. They bind tightly to the ASIALOGLYCOPROTEIN RECEPTOR which is located on hepatocyte plasma membranes. After internalization by adsorptive ENDOCYTOSIS they are delivered to LYSOSOMES for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with HEPATIC CIRRHOSIS or HEPATITIS.

Top Publications

  1. Yuita H, Tsuiji M, Tajika Y, Matsumoto Y, Hirano K, Suzuki N, et al. Retardation of removal of radiation-induced apoptotic cells in developing neural tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos. Glycobiology. 2005;15:1368-75 pubmed
    ..These results strongly suggest that MGL1/CD301a is involved in the clearance of apoptotic cells. This process should be essential in the repair and normal development of X-ray-irradiated embryos. ..
  2. Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami T, Hedrick S, et al. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 2002;277:28892-901 pubmed
    ..These two lectins may function cooperatively as recognition and endocytic molecules on macrophages and related cells. ..
  3. Raes G, Brys L, Dahal B, Brandt J, Grooten J, Brombacher F, et al. Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation. J Leukoc Biol. 2005;77:321-7 pubmed
    ..Moreover, we show that expression of MGL on human monocytes is also up-regulated by IL-4. Hence, macrophage galactose-type C-type lectins represent novel surface markers for murine and human aaMF...
  4. Xu W, Cao L, Chen L, Li J, Zhang X, Qian H, et al. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res. 2011;17:3783-93 pubmed publisher
    ..It is likely clinically useful in diagnosis and monitoring of HCC and may have a role in clinical decision making. ..
  5. Singh S, Streng Ouwehand I, Litjens M, Weelij D, García Vallejo J, van Vliet S, et al. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol. 2009;46:1240-9 pubmed publisher
    ..Strikingly, MGL2 interacted strongly to adenocarcinoma cells, suggesting a potential role in tumor immunity. ..
  6. Sato K, Imai Y, Higashi N, Kumamoto Y, Onami T, Hedrick S, et al. Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a. Blood. 2005;106:207-15 pubmed
    ..Taken together, MGL1 expressed on a specific subpopulation of macrophages that secrete IL-1alpha was proposed to regulate specific cellular interactions crucial to granulation tissue formation. ..
  7. Kumamoto Y, Higashi N, Denda Nagai K, Tsuiji M, Sato K, Crocker P, et al. Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin 1. J Biol Chem. 2004;279:49274-80 pubmed
    ..These results suggest that Sn acts as an endogenous counter-receptor for MGL1. ..
  8. Ellinger I, Klapper H, Courtoy P, Vaerman J, Fuchs R. Different temperature sensitivity of endosomes involved in transport to lysosomes and transcytosis in rat hepatocytes: analysis by free-flow electrophoresis. Electrophoresis. 2002;23:2117-29 pubmed
  9. Sato K, Imai Y, Higashi N, Kumamoto Y, Mukaida N, Irimura T. Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation. Int Immunol. 2005;17:559-68 pubmed
    ..Results suggest that MGL1/2-positive cells represent a distinct sub-population of macrophages, having unique functions in the generation and maintenance of granulation tissue induced by antigenic stimuli. ..

More Information

Publications62

  1. Lumeng C, Delproposto J, Westcott D, Saltiel A. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008;57:3239-46 pubmed publisher
  2. Onami T, Lin M, Page D, Reynolds S, Katayama C, Marth J, et al. Generation of mice deficient for macrophage galactose- and N-acetylgalactosamine-specific lectin: limited role in lymphoid and erythroid homeostasis and evidence for multiple lectins. Mol Cell Biol. 2002;22:5173-81 pubmed
    ..Experiments are presented that indicate the existence of another galactose- and N-acetylgalactosamine-recognizing lectin distinct from mMGL. This may explain the absence of a strong phenotype in mMGL-deficient mice. ..
  3. Dupasquier M, Stoitzner P, Wan H, Cerqueira D, van Oudenaren A, Voerman J, et al. The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. J Leukoc Biol. 2006;80:838-49 pubmed
    ..Taken together, these data suggest that the dermal microenvironment induces mononuclear phagocyte subpopulations to express mMGL and possibly other markers of alternatively activated macrophages, independent of IL-4/IL-13 signaling. ..
  4. Saba K, Denda Nagai K, Irimura T. A C-type lectin MGL1/CD301a plays an anti-inflammatory role in murine experimental colitis. Am J Pathol. 2009;174:144-52 pubmed publisher
    ..These results strongly suggest that MGL1/CD301a plays a protective role against colitis by effectively inducing IL-10 production by colonic lamina propria macrophages in response to invading commensal bacteria. ..
  5. Seow Y, Tan M, Woo K. Expression of a functional asialoglycoprotein receptor in human renal proximal tubular epithelial cells. Nephron. 2002;91:431-8 pubmed
    ..Primary renal proximal tubular epithelial cells have a functional ASGPR, consisting of the H1 and H2 subunits, that is capable of specific ligand binding and uptake. ..
  6. Jankovic M, Vicovac L. A specific wheat germ agglutinin-immunoreactive protein in human placenta. Comp Biochem Physiol B Biochem Mol Biol. 2000;127:135-46 pubmed
    ..The placental protein having molecular mass of 66 kD was identified as specific. The protein of 66 kD was characterized as a calcium-dependent, asialofetuin-binding molecule. ..
  7. Vukman K, Ravidà A, Aldridge A, O Neill S. Mannose receptor and macrophage galactose-type lectin are involved in Bordetella pertussis mast cell interaction. J Leukoc Biol. 2013;94:439-48 pubmed publisher
    ..Syk was involved in the CLR-mediated activation of mast cells by BP. Bacterial recognition by immune cells has been predominantly attributed to TLRs; in this study, the novel role of CLRs in the BP-mast cell interaction is highlighted. ..
  8. Hiki Y, Takahashi K, Shimozato S, Odani H, Yamamoto K, Tomita M, et al. Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1. Clin Exp Nephrol. 2008;12:20-7 pubmed publisher
    ..016). These results suggest that the anti-IgA1 hinge peptide antibody plays a role in the inhibition of glomerular IgA deposition. ..
  9. Sangeetha S, Appukuttan P. IgA1 is the premier serum glycoprotein recognized by human galectin-1 since T antigen (Galbeta1-->3GalNAc-) is far superior to non-repeating N-acetyl lactosamine as ligand. Int J Biol Macromol. 2005;35:269-76 pubmed
  10. Eichinger D. A role for a galactose lectin and its ligands during encystment of Entamoeba. J Eukaryot Microbiol. 2001;48:17-21 pubmed
    ..These results suggest a new role for the Entamoeba gal lectins in monitoring the concentrations of gal ligands in the colon and contributing to stimuli that induce encystment...
  11. Furukawa T, Ozawa M, Huang R, Muramatsu T. A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells: cDNA cloning and sequence analysis. J Biochem. 1990;108:297-302 pubmed
    ..We propose that HBP-44 is extruded from plasma membranes and interacts with heparin and related molecules and that it is involved in the interactions of plasma membranes with basement membranes. ..
  12. Ahmed H, Pohl J, Fink N, Strobel F, Vasta G. The primary structure and carbohydrate specificity of a beta-galactosyl-binding lectin from toad (Bufo arenarum Hensel) ovary reveal closer similarities to the mammalian galectin-1 than to the galectin from the clawed frog Xenopus laevis. J Biol Chem. 1996;271:33083-94 pubmed
    ..laevis 16-kDa galectin, clearly constitute distinct subgroups in the extant amphibian taxa and may have diverged early in the evolution of chordate lineages. ..
  13. Vázquez Martin C, Gil Martín E, Fernández Briera A. Elevation of ST6Gal I activity in malignant and transitional tissue in human colorectal cancer. Oncology. 2005;69:436-44 pubmed
    ..This work reports enhanced ST6Gal I activity in tumor and transitional tissues from CRC patients. However, our overall results suggest that ST6Gal I activity is not indicative of the patient's outcome. ..
  14. Black P, McKinnon K, Wooden S, Ussery M. Antiviral activity of biological response modifiers in a murine model of AIDS. Requirement for augmentation of natural killer cell activity and synergy with oral AZT. Int J Immunopharmacol. 1996;18:633-50 pubmed
    ..NK cells thus appear to play a key role in resistance to this retrovirus, as has been suggested for HIV. ..
  15. Díez S, Miguéliz I, Tros de Ilarduya C. Targeted cationic poly(D,L-lactic-co-glycolic acid) nanoparticles for gene delivery to cultured cells. Cell Mol Biol Lett. 2009;14:347-62 pubmed publisher
  16. Upham J, Pickett D, Irimura T, Anders E, Reading P. Macrophage receptors for influenza A virus: role of the macrophage galactose-type lectin and mannose receptor in viral entry. J Virol. 2010;84:3730-7 pubmed publisher
  17. Streng Ouwehand I, Ho N, Litjens M, Kalay H, Boks M, Cornelissen L, et al. Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells. elife. 2016;5: pubmed publisher
    ..We conclude that controlled neo-glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. ..
  18. Kübler D, Hung C, Dam T, Kopitz J, Andre S, Kaltner H, et al. Phosphorylated human galectin-3: facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy. Biochim Biophys Acta. 2008;1780:716-22 pubmed publisher
    ..Spectroscopically, phosphorylation induced alterations in the far UV CD, indicative of an increase in ordered structure. This is accompanied by changes in the environment of aromatic amino acids signified by shifts in the near UV CD. ..
  19. Biessen E, Sliedregt Bol K, T Hoen P, Prince P, Van der Bilt E, Valentijn A, et al. Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes. Bioconjug Chem. 2002;13:295-302 pubmed
  20. Clemens D, Halgard C, Cole J, Miles R, Sorrell M, Tuma D. Impairment of the asialoglycoprotein receptor by ethanol oxidation. Biochem Pharmacol. 1996;52:1499-505 pubmed
    ..These results indicated that ethanol oxidation was required for the ethanol-induced impairment in ligand binding, and that the reduced ligand binding was a result of a decrease in the ability of the ligand to bind to the receptor. ..
  21. Ohshita T, Nikawa T, Towatari T, Katunuma N. Effects of selective inhibition of cathepsin B and general inhibition of cysteine proteinases on lysosomal proteolysis in rat liver in vivo and in vitro. Eur J Biochem. 1992;209:223-31 pubmed
    ..These results shows that E-64-sensitive cysteine proteinases are important in lysosomal protein degradation, but cathepsin B has only a role in part and that an E-64-resistant proteinase(s) may also be important. ..
  22. Saxena A, Yik J, Weigel P. H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid. J Biol Chem. 2002;277:35297-304 pubmed
    ..Nonetheless, these results raise the intriguing possibility that naturally occurring H2 homo-oligomers may exist in human hepatocytes and have an as yet undiscovered function. ..
  23. Tian X, Baek K, Shin I. Dual-labeled glycoclusters: synthesis and their application in monitoring lectin-mediated endocytosis. Mol Biosyst. 2013;9:978-86 pubmed publisher
    ..The results of these efforts show that the novel dual-labeled neoglycopeptides are effective fluorescence and MR imaging agents for monitoring biological processes associated with lectins. ..
  24. Treichel U, Meyer zum Buschenfelde K, Dienes H, Gerken G. Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol. 1997;142:493-8 pubmed
    ..These results suggest that the ASGPR is capable of specifically binding HBV-particles and, moreover, to mediate their hepatic endocytosis which ultimately could be responsible for the HBV-infection of liver cells. ..
  25. Dam T, Gabius H, Andre S, Kaltner H, Lensch M, Brewer C. Galectins bind to the multivalent glycoprotein asialofetuin with enhanced affinities and a gradient of decreasing binding constants. Biochemistry. 2005;44:12564-71 pubmed
    ..These findings have important implications for the binding of galectins to multivalent carbohydrate receptors. ..
  26. Takei R, Suzuki D, Hoshiba T, Nagaoka M, Seo S, Cho C, et al. Role of E-cadherin molecules in spheroid formation of hepatocytes adhered on galactose-carrying polymer as an artificial asialoglycoprotein model. Biotechnol Lett. 2005;27:1149-56 pubmed
    ..As a result, E-cadherin could play an important role in hepatocyte assembly. ..
  27. Ren T, Zhang G, Liu D. Synthesis of galactosyl compounds for targeted gene delivery. Bioorg Med Chem. 2001;9:2969-78 pubmed
    ..These results provide direct evidence in support of our new strategy for the use of small and synthetic compounds for cell specific and targeted gene delivery. ..
  28. Lönnberg M, Carlsson J. Membrane assisted isoform immunoassay. A rapid method for the separation and determination of protein isoforms in an integrated immunoassay. J Immunol Methods. 2000;246:25-36 pubmed
    ..1 unit difference in pI. The results indicate that the technique should be useful for rapid point-of-care testing of clinically interesting charged protein isoforms. ..
  29. Schwan R, Malet L, Loiseaux M, Llorca P. Which types of alcohol-use disorder will asialotransferrin detect?. Clin Chem. 2004;50:782 pubmed
  30. Van T Veer C, van der Poll T. Keeping blood clots at bay in sepsis. Nat Med. 2008;14:606-8 pubmed publisher
  31. De Guzman J, Soper S, McCarley R. Assessment of glycoprotein interactions with 4-[(2-aminoethyl)carbamoyl]phenylboronic acid surfaces using surface plasmon resonance spectroscopy. Anal Chem. 2010;82:8970-7 pubmed publisher
    ..Importantly, it is demonstrated that use of tris(hydroxymethyl)aminomethane buffer allows for decreased secondary interactions of nonglycosylated proteins on the AECPBA/dextran surface, as noted with the model protein ExtrAvidin. ..
  32. Mizuochi S, Akimoto Y, Imai Y, Hirano H, Irimura T. Immunohistochemical study on a macrophage calcium-type lectin in mouse embryos: transient expression in chondroblasts during endochondral ossification. Glycoconj J. 1998;15:397-404 pubmed
    ..These results provide first evidence showing the expression of MMGL in cells other than macrophages. ..
  33. Ogino A, Takemura G, Kawasaki M, Tsujimoto A, Kanamori H, Li L, et al. Erythropoietin receptor signaling mitigates renal dysfunction-associated heart failure by mechanisms unrelated to relief of anemia. J Am Coll Cardiol. 2010;56:1949-58 pubmed publisher
  34. Tancred L, Telepnev M, Golovliov I, Andersson B, Andersson H, Lindgren H, et al. Administration of a nitric oxide donor inhibits mglA expression by intracellular Francisella tularensis and counteracts phagosomal escape and subversion of TNF-? secretion. J Med Microbiol. 2011;60:1570-83 pubmed publisher
    ..tularensis LVS but led to containment of the bacteria in the phagosome. Moreover, the treatment resulted in modification by nitration of several F. tularensis proteins. ..
  35. Oo Puthinan S, Maenuma K, Sakakura M, Denda Nagai K, Tsuiji M, Shimada I, et al. The amino acids involved in the distinct carbohydrate specificities between macrophage galactose-type C-type lectins 1 and 2 (CD301a and b) of mice. Biochim Biophys Acta. 2008;1780:89-100 pubmed
    ..MGL1 mutants of Ala89Arg and Ala89Arg/Pro115Arg showed beta-GalNAc bindings. Molecular modeling illustrated potential direct molecular interactions of Leu61, Arg89, and His109 in MGL2 CRD with GalNAc. ..
  36. Ikarashi N, Toba K, Kato K, Ozawa T, Oda M, Takayama T, et al. Erythropoietin, but not asialoerythropoietin or carbamyl-erythropoietin, attenuates monocrotaline-induced pulmonary hypertension in rats. Clin Exp Hypertens. 2012;34:575-81 pubmed publisher
    ..We conclude that lungs may express EPOR homoreceptors, but not heteroreceptors. Adequate serum erythropoietin levels may be essential for pulmonary protective effects. ..
  37. Bianchi V, Raspagni A, Arfini C, Vidali M. High performance liquid chromatography evaluation of serum carbohydrate-deficient transferrin and more sialylated transferrin glycoforms in children. Scand J Clin Lab Invest. 2012;72:274-80 pubmed publisher
    ..3% and 6.4% may be suggested as upper limits of normal range to detect increases of Disialo- and Trisialo-Tf. The presence of Asialo- and Monosialo-Tf should be considered an abnormal finding and prompt further investigations. ..
  38. Comelli E, Guggenheim B, Stingele F, Neeser J. Selection of dairy bacterial strains as probiotics for oral health. Eur J Oral Sci. 2002;110:218-24 pubmed
    ..sobrinus OMZ176. These findings encourage further research with selected non-pathogenic dairy bacterial strains with the aim to decrease the cariogenic potential of dental plaque...
  39. Murray J, Sarkar S, Wolkoff A. Single vesicle analysis of endocytic fission on microtubules in vitro. Traffic. 2008;9:833-847 pubmed publisher
    ..A single round of fission resulted in 6.5-fold purification of ntcp from ASOR, and 25% of the resulting vesicles were completely depleted of the endocytic ligand. ..
  40. Velásquez J, Canovas S, Barajas P, Marcos J, Jimenez Movilla M, Gallego R, et al. Role of sialic acid in bovine sperm-zona pellucida binding. Mol Reprod Dev. 2007;74:617-28 pubmed
    ..From this last result we hypothesize that a neuraminidase from cortical granules would probably participate in the block to polyspermy by removing sialic acid from the ZP. ..
  41. Parsons J, Altmann F, Arrenberg C, Koprivova A, Beike A, Stemmer C, et al. Moss-based production of asialo-erythropoietin devoid of Lewis A and other plant-typical carbohydrate determinants. Plant Biotechnol J. 2012;10:851-61 pubmed publisher
  42. Dawson R, Paddle B, Alderton M. Characterization of the Asialofetuin microtitre plate-binding assay for evaluating inhibitors of ricin lectin activity. J Appl Toxicol. 1999;19:307-12 pubmed
    ..The assay permits qualitative comparison of inhibitors of ricin B-chain lectin activity. ..
  43. Chiricolo M, Malagolini N, Bonfiglioli S, Dall Olio F. Phenotypic changes induced by expression of beta-galactoside alpha2,6 sialyltransferase I in the human colon cancer cell line SW948. Glycobiology. 2006;16:146-54 pubmed
    ..These data indicate that in the cell line SW948, the effect of ST6Gal.I expression is consistent with the attenuation of the neoplastic phenotype. ..
  44. Chwalek M, Auzély R, Fort S. Synthesis and biological evaluation of multivalent carbohydrate ligands obtained by click assembly of pseudo-rotaxanes. Org Biomol Chem. 2009;7:1680-8 pubmed publisher
    ..Their ability to inhibit the binding of Arachis hypogaea agglutinin to asialofetuin, assayed by enzyme linked lectin assays (ELLA), was shown to be valency-dependent. ..
  45. Shah M, Fujiyama K, Flynn C, Joshi L. Sialylated endogenous glycoconjugates in plant cells. Nat Biotechnol. 2003;21:1470-1 pubmed
    ..Here we report the presence of sialylated glycoconjugates in suspension-cultured cells of Arabidopsis thaliana and suggest that a genetic and enzymatic basis for sialylation exists in plants. ..
  46. Chuang V, Hijioka M, Katsuki M, Nishi K, Hara T, Kaneko K, et al. Characterization of benzodiazepine binding site on human alpha1-acid glycoprotein using flunitrazepam as a photolabeling agent. Biochim Biophys Acta. 2005;1725:385-93 pubmed
    ..Similarly, FNZP did not show a difference in binding affinity to the two genetic variants of hAGP. Sequence analysis of the photolabeled peptide indicated a sequence corresponding to Tyr91-Arg105 of hAGP. ..
  47. Grewal P, Uchiyama S, Ditto D, Varki N, Le D, Nizet V, et al. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med. 2008;14:648-55 pubmed publisher
    ..Hemostatic adaptation by the Ashwell receptor moderates the onset and severity of disseminated intravascular coagulation during sepsis and improves the probability of host survival. ..
  48. Vanderver A, Schiffmann R, Timmons M, Kellersberger K, Fabris D, Hoffman E, et al. Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease. Clin Chem. 2005;51:2031-42 pubmed
    ..The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease. ..
  49. Braun J, Willnow T, Ishibashi S, Ashwell G, Herz J. The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit. J Biol Chem. 1996;271:21160-6 pubmed
    ..the sinusoidal membrane of hepatocytes where it binds and endocytoses galactose-terminated glycoproteins (asialoglycoproteins). ASGPR is composed of two highly homologous subunits, termed hepatic lectin 1 and 2...
  50. van t Hooft F, Dallinga Thie G, van Tol A. Leupeptin as a tool for the detection of the sites of catabolism of rat high-density lipoprotein apolipoproteins A-I and E. Biochim Biophys Acta. 1985;834:75-84 pubmed
  51. Geffen I, Fuhrer C, Spiess M. Endocytosis by the asialoglycoprotein receptor is independent of cytoplasmic serine residues. Proc Natl Acad Sci U S A. 1991;88:8425-9 pubmed
    ..Analysis of individual serine mutations identified serine-12 of subunit H2 as the major site of phosphorylation in the ASGP receptor. ..
  52. Ise H, Sugihara N, Negishi N, Nikaido T, Akaike T. Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes. Biochem Biophys Res Commun. 2001;285:172-82 pubmed
  53. Kitamura T, Garofalo R, Kamijo A, Hammond D, Oka J, Caflisch C, et al. Human intestinal epithelial cells express a novel receptor for IgA. J Immunol. 2000;164:5029-34 pubmed
    ..The function of this novel IgA receptor in mucosal immunity remains to be elucidated. ..