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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TLDR
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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Eukaryotic protein glycosylation: a primer for histochemists and cell biologists.
TL;DR: Following this educational survey, examples where known biological function is related to the glycan structures carried by proteins are given and mucins and their glycosylation patterns are considered as instructive proof-of-principle case.
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Recent advancements in understanding mammalian O-mannosylation.
TL;DR: This review will focus on recent discoveries delineating the various enzymes, structures and functions associated with O-mannose-initiated glycoproteins, and discusses the evolution of this pathway.
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GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis
Raquel Planas,Radleigh G. Santos,Paula Tomas-Ojer,Carolina Cruciani,Andreas Lutterotti,Wolfgang Faigle,Nicole Schaeren-Wiemers,Carmen Espejo,Herena Eixarch,Clemencia Pinilla,Roland Martin,Mireia Sospedra +11 more
TL;DR: GDP-l-fucose synthase is an autoantigen recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients with multiple sclerosis, and the possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis is suggested.
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Low-density lipoprotein receptor-related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation.
Dina Safina,Frederik Schlitt,Ramona Romeo,Thorsten Pflanzner,Claus U. Pietrzik,Vasanthy Narayanaswami,Frank Edenhofer,Andreas Faissner +7 more
TL;DR: It is shown that LeX‐glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS, suggesting that LRP 1 facilitates NSPCs differentiation via interaction with apolipoprotein E (ApoE).
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Glycosylation with ribitol-phosphate in mammals: New insights into the O-mannosyl glycan.
Hiroshi Manya,Tamao Endo +1 more
TL;DR: O-mannosyl glycan has a novel, unique structure that is important for the maintenance of brain and muscle functions that has opened up a new field in glycoscience.
References
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Journal ArticleDOI
α1,3-Fucosyltransferase IX (Fut9) determines Lewis X expression in brain
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TL;DR: Results showed that Fut9 is the most responsible enzyme for the synthesis of Lex in brain, and the developmental profile of activity for thehesis of Lex was well correlated with that of Fut9 transcript.
Journal ArticleDOI
Receptor Tyrosine Phosphatase β (RPTPβ) Activity and Signaling Are Attenuated by Glycosylation and Subsequent Cell Surface Galectin-1 Binding
TL;DR: GnT-Vb activity promotes the addition of the O-mannosyl-linked HNK-1 modification found on the developmentally regulated and neuron-specific receptor protein-tyrosine phosphatase β (RPTPβ).
Journal ArticleDOI
Protein O-mannosylation is crucial for E-cadherin–mediated cell adhesion
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