Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ.
Shohei Yaji,Hiroshi Manya,Naoki Nakagawa,Hiromu Takematsu,Tamao Endo,Reiji Kannagi,Toru Yoshihara,Masahide Asano,Shogo Oka +8 more
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The results revealed the importance of O-mannosylated glycan chains in the presentation of functional glycan epitopes in the brain.Abstract:
Glycosylation is a major protein modification. Although proteins are glycosylated/further modulated by several glycosyltransferases during trafficking from the endoplasmic reticulum to the Golgi apparatus, a certain glycan epitope has only been detected on a limited number of proteins. Of these glycan epitopes, Lewis X is highly expressed in the early stage of a developing brain and plays important roles in cell-cell interaction. The Lewis X epitope is comprised of a trisaccharide (Galβ1-4 (Fucα1-3) GlcNAc), and a key enzyme for the expression of this epitope is α1,3-fucosyltransferase 9. However, the scaffolding glycan structure responsible for the formation of the Lewis X epitope as well as its major carrier protein has not been fully characterized in the nervous system. Here we showed that the Lewis X epitope was mainly expressed on phosphacan/receptor protein tyrosine phosphatase β (RPTPβ) in the developing mouse brain. Expression of the Lewis X epitope was markedly reduced in β1,4-galactosyltransferase 2 (β4GalT2) gene-deficient mice, which indicated that β4GalT2 is a major galactosyltransferase required for the Lewis X epitope. We also showed that the Lewis X epitope almost disappeared due to the knockout of protein O-mannose β1,2-N-acetylglucosaminyltransferase 1, an N-acetylglucosaminyltransferase essential for the synthesis of O-mannosylated glycans, which indicated that the O-mannosylated glycan is responsible for presenting the Lewis X epitope. Since O-mannosylated glycans on phosphacan/RPTPβ could also present human natural killer-1, another glycan epitope specifically expressed in the nervous system, our results revealed the importance of O-mannosylated glycan chains in the presentation of functional glycan epitopes in the brain.read more
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The restricted nature of protein glycosylation in the mammalian brain
Sarah W Williams,Sarah W Williams,Maxence Noel,Sylvain Lehoux,Murat Cetinbas,Ramnik J. Xavier,Ruslan I. Sadreyev,Edward M. Scolnick,Jordan W. Smoller,Richard D. Cummings,Robert G. Mealer,Robert G. Mealer,Robert G. Mealer +12 more
TL;DR: It is hypothesized that the restricted repertoire of protein glycans arises from their tight regulation in the brain, and analysis of all glycosylation genes in humans showed a global downregulation in theBrain glycans correlate with RNA expression of their synthetic enzymes, and
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An embeddable molecular code for Lewis X modification through interaction with fucosyltransferase 9
TL;DR: In this paper , a contiguous 29-amino acid sequence in the N-terminal domain of LAMP-1 is shown to be responsible for promotion of the FUT9-catalyzed Lewis X modification.
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