Disease relevance of polylactosamine

• Branching beta 1-6N-acetylglucosaminetransferases and polylactosamine expression in mouse F9 teratocarcinoma cells and differentiated counterparts [1].
• UDP-N-acetylglucosamine:alpha-6-d-mannoside beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-TV) is a regulator of polylactosamine-containing N-glycans and is causally involved in T cell regulation and tumor metastasis [2].
• B-1 cell (CD5+B220+) outgrowth in murine schistosomiasis is genetically restricted and is largely due to activation by polylactosamine sugars [3].
• Phaseolus vulgaris leukoagglutinin (L-PHA) requires the beta 1-6-linked lactosamine antenna for high-affinity binding and was used histochemically to characterize the distribution of these sugar structures in human esophageal squamous cell carcinomas from 42 patients [4].
• Fucosylated type-2 chain polylactosamine antigens in human lung cancer [5].

High impact information on polylactosamine

• To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Gal alpha-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the alpha-1,2-fucosyl lactosamine moiety (H-epitope) [6].
• (b) Differences in mass were due primarily to variation in carbohydrate moieties, including sulfated aspargine-linked glycopeptides (GP), chondroitin sulfate (CS), and heparan sulfate (HS) glycosaminoglycans, as well as O-linked mucin and polylactosamine structure(s) [7].
• Here we present evidence that laminin is a major glycoprotein ligand for L-14 in differentiating mouse C2C12 muscle cells and that binding of secreted L-14 to polylactosamine oligosaccharides of substrate laminin induces loss of cell-substratum adhesion [8].
• The ligand for one of these proteins, E-selectin (LECAM-2, ELAM-1) has been described by several groups to contain a polylactosamine structure bearing a terminal sialic acid residue and at least one fucose residue [9].
• The enzyme defect in most HEMPAS patients has previously been proposed as a lowered activity of N-acetylglucosaminyltransferase II, resulting in a lack of polylactosamine on proteins and leading to the accumulation of polylactosaminyl lipids [10].

Chemical compound and disease context of polylactosamine

• beta-All-trans-retinoic acid (RA)-induced endodermal differentiation of mouse F9 teratocarcinoma cells is accompanied by changes in glycoprotein glycosylation, including expression of i antigen (i.e. polylactosamine) and leukophytohemagglutinin-reactive oligosaccharides (i.e. -GlcNAc beta 1-6Man alpha 1-6-branched N-linked) [1].
• FAB-MS characterization of sialyl Lewis x determinants on polylactosamine chains of human airway mucins secreted by patients suffering from cystic fibrosis or chronic bronchitis [11].
• [3H]Mannose- and [3H]glucosamine-labeled lactosamine-type glycopeptides of Semliki Forest virus membrane proteins were stripped of their fucose, sialic acid, galactose and distal N-acetylglucosamine residues and subsequently digested with endo-beta-D-N-acetylglucosaminidase D from Diplococcus pneumoniae [12].

Biological context of polylactosamine

• The loss of sialic acid and polylactosamine sequences in glycosylation mutants of MDAY-D2 has been correlated previously with enhanced cell adhesion on extracellular matrix proteins [13].
• Our results indicate that addition of sulfate esters, terminal alpha-Gal residues, polylactosamine chains, outer-branch fucose residues, some initial phosphorylation, and most phosphodiester processing may occur beyond a compartment where some beta-Gal and sialic acid residues can be added [14].
• This phenomenon is reproducible by stable expression of ST6Gal I in parental CHO cells, but not upon transfection of the competing lactosamine-specific alpha2-3-sialyltransferase (Galbeta1-(3)4GlcNAc:alpha2-3-sialyltransferase; (ST6Gal III) formerly ST3N) into either cell type [15].
• The results suggest that polylactosamine (keratan) glycoconjugates of high molecular weight are associated with the plasma membranes of meiotic and haploid male germ cells [16].
• Lumican with polylactosamine (nonsulfated keratan sulfate) side chains was detected in extracts of corneas as early as day 7 of embryonic development, and continued to accumulate within the cornea through day 18 [17].

Anatomical context of polylactosamine

• The plasma membrane glycoproteins of the class 2 mutants were similar to those of MDAY-D2 cells including the presence of sialylated polylactosamine-containing antennae in the asparagine-linked oligosaccharide [18].
• Stage-specific expression of cancer-associated type 1 and type 2 chain polylactosamine antigens in the developing pancreas of human embryos [19].
• Affinity-purified human galectin-1 was found to bind to purified polylactosamine-containing glycoproteins and to detergent-solubilized cellular proteins electroblotted onto nitrocellulose membranes [20].
• Chemical cross-linking experiments have identified binding of endogenous cell-surface Mac-2 to three glycoproteins of molecular masses of 92, 125, and 180 kDa containing alpha-galactosyl and polylactosamine structures on thioglycollate-elicited macrophages [21].
• Mouse GM979 erythroleukemic cells were found to synthesize the branched form of erythroglycan, a large polylactosamine structure known to be attached to band 3 and possibly to other proteins on human erythrocytes [22].

Associations of polylactosamine with other chemical compounds

• Also, unlike hCD33, mCD33 did not bind to alpha2-3- or alpha2-6-linked sialic acids on lactosamine units [23].
• Enzymatic removal of sialic acid, polylactosamine, or complete asparagine-linked chains from purified P2B enhanced its binding to collagen, laminin, and fibronectin [13].
• Fuc-TVII can efficiently utilize alpha-2,3-sialyllactosamine in vitro to form the sialyl Lewis x tetrasaccharide but does not utilize lactosamine to form the Lewis x moiety [24].
• The complementary in vitro acceptor site-specificities of Fuc-TIV and Fuc-TVII imply that these enzymes cooperate in vivo in the biosynthesis of monosialylated, multifucosylated polylactosamine components of selectin counterreceptors on human leukocytes [25].
• The action of core 2 GlcNAc-transferase followed by beta 1-4Gal-transferase provides an N-acetyllactosamine antenna that can be extended with polylactosamine (i.e. repeating Gal beta 1-4GlcNAc beta 1-3) provided UDP-GlcNAc:Gal beta-R beta 1-3GlcNAc-transferase (GlcNAc-transferase) (i)) activity is present [26].

Gene context of polylactosamine

• (formula; see text) To understand the structural basis of F. nucleatum binding, we screened glycolipids and neoglycolipids carrying carbohydrate structures related to those of the PRG for receptor activity; components with unsubstituted terminal lactosamine residues best supported adherence [27].
• The results showed that the single CD52 N-glycosylation site is occupied by large sialylated, polylactosamine-containing, core-fucosylated tetraantennary oligosaccharides [28].
• The O-linked glycans, which were estimated to comprise approximately 85% of the total sugars on gelatinase B, mainly consisted of type 2 cores with Galbeta1,4GlcNAc (lactosamine) extensions, with or without sialic acid or outer arm fucose [29].
• TNF-alpha increases the carbohydrate sulfation of CD44: induction of 6-sulfo N-acetyl lactosamine on N- and O-linked glycans [30].
• Moreover, alpha1,3-Fut activity toward a polylactosamine chain in homogenates of brain tissues and primary cultured cells showed a pattern typical of Fut9, not Fut4 [31].

Analytical, diagnostic and therapeutic context of polylactosamine

• The results obtained from treatment of each isoform with endo-beta-galactosidase and neuraminidases and from lectin affinity chromatography reveal that MPR-2A contains a linear polylactosamine sequence(s) comprised of approximately 5 lactosamine units [32].
• Sialylated polylactosamine structures were identified and quantified by analyzing high performance liquid chromatography profiles of oligosaccharides first released by peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase and then treated with endo-beta-galactosidase, using a single, stained band of recombinant erythropoietin [33].
• We have separated polylactosamine-containing gelatin-binding fragments of placental fibronectin from their counterparts containing smaller "complex" N-linked saccharides using Sephadex G-200 gel permeation chromatography [34].
• Molecular cloning of a novel alpha2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids [35].
• Immunochemical stainings with monoclonal antibodies against functionally active decorated L-selectin ligands. i.e., sialyl-Lewis x (sLex, 2F3 and HECA-452) or sulfated lactosamine (MECA-79) were performed [36].

References