title: Poly-N-acetyllactosamine extension in N-glycans and core 2- and core 4-branched O-glycans is differentially controlled by i-extension enzyme and different members of the beta 1,4-galactosyltransferase gene family.
abstract: Poly-N-acetyllactosamines are attached to N-glycans, O-glycans, and glycolipids and serve as underlying glycans that provide functional oligosaccharides such as sialyl Lewis(X). Poly-N-acetyllactosaminyl repeats are synthesized by the alternate addition of beta1,3-linked GlcNAc and beta1,4-linked Gal by i-extension enzyme (iGnT) and a member of the beta1,4-galactosyltransferase (beta4Gal-T) gene family. In the present study, we first found that poly-N-acetyllactosamines in N-glycans are most efficiently synthesized by beta4Gal-TI and iGnT. We also found that iGnT acts less efficiently on acceptors containing increasing numbers of N-acetyllactosamine repeats, in contrast to beta4Gal-TI, which exhibits no significant change. In O-glycan biosynthesis, N-acetyllactosamine extension of core 4 branches was found to be synthesized most efficiently by iGnT and beta4Gal-TI, in contrast to core 2 branch synthesis, which requires iGnT and beta4Gal-TIV. Poly-N-acetyllactosamine extension of core 4 branches is, however, less efficient than that of N-glycans or core 2 branches. Such inefficiency is apparently due to competition between a donor substrate and acceptor in both galactosylation and N-acetylglucosaminylation, since a core 4-branched acceptor contains both Gal and GlcNAc terminals. These results, taken together, indicate that poly-N-acetyllactosamine synthesis in N-glycans and core 2- and core 4-branched O-glycans is achieved by iGnT and distinct members of the beta4Gal-T gene family. The results also exemplify intricate interactions between acceptors and specific glycosyltransferases, which play important roles in how poly-N-acetyllactosamines are synthesized in different acceptor molecules.
authors.affiliation: Glycobiology Program, Cancer Research Center, the Burnham Institute, La Jolla, California 92037, USA. minoru@burnham-inst.org
authors.forename: M
authors.initials: M
authors.lastname: Ujita
authors.forename: A K
authors.initials: AK
authors.lastname: Misra
authors.forename: J
authors.initials: J
authors.lastname: McAuliffe
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D019556:COS Cells; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D009077:Mucins; D009844:Oligosaccharides; D011134:Polysaccharides; C037199:poly-N-acetyllactosamine; C106501:N-acetylglucosaminyltransferase IGnT; D005700:Galactosyltransferases; D017351:N-Acetylglucosaminyltransferases