Neurons and Glia Modify Receptor Protein-tyrosine Phosphatase ζ (RPTPζ)/Phosphacan with Cell-specific O-Mannosyl Glycans in the Developing Brain

Dwyer, Chrissa A.; Katoh, Toshihiko; Tiemeyer, Michael; Matthews, Russell T.

doi:10.1074/jbc.m114.614099

Cited by 33 publications

(25 citation statements)

References 64 publications

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“…However, each cell type synthesizes a unique repertoire of glycan structures and glycoconjugates. For example, different antibody epitopes on different glycoforms of phosphacan label different types of cells in the developing cerebral cortex (Dwyer et al, 2015), supporting the idea that glycoform specialization may tailor protein function at the cellular level in the brain. Additional complexity arises from changes in the expression of different glycans and glycoconjugates in different brain regions and across developmental stages (Matthews et al, 2002; Morawski et al, 2012; Torii et al, 2014).…”

Section: Introductionmentioning

confidence: 86%

“…POMGnT1 catalyzes the elaboration of core M1 and M2 glycans on dystroglycan (Stalnaker et al, 2010) and other extracellular proteins such as phosphacan (Dwyer et al, 2012, 2015), CD-24 (Bleckmann et al, 2009) and Cadherins (Vester-Christensen et al, 2013). Interestingly loss of POMGnT1 activity affects the production of dystroglycan carrying the Large-glycan modification that is capable of functioning as an ECM receptor, suggesting a common glycosylation pathway.…”

Section: The Dystrophin Glycoprotein Complexmentioning

confidence: 99%

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Glycan susceptibility factors in autism spectrum disorders

Dwyer

2016

Molecular Aspects of Medicine

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Idiopathic autism spectrum disorders (ASDs) are neurodevelopmental disorders with unknown etiology. An estimated 1:68 children in the U.S. are diagnosed with ASDs, making these disorders a substantial public health issue. Recent advances in genome sequencing have identified numerous genetic variants across the ASD patient population. Many genetic variants identified occur in genes that encode glycosylated extracellular proteins (proteoglycans or glycoproteins) or enzymes involved in glycosylation (glycosyltransferases and sulfotransferases). It remains unknown whether “glycogene” variants cause changes in glycosylation and whether they contribute to the etiology and pathogenesis of ASDs. Insights into glycan susceptibility factors are provided by studies in the normal brain and congenital disorders of glycosylation, which are often accompanied by ASD-like behaviors. The purpose of this review is to present evidence that supports a contribution of extracellular glycans and glycoconjugates to the etiology and pathogenesis of idiopathic ASDs and other types of pervasive neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 86%

Section: The Dystrophin Glycoprotein Complexmentioning

confidence: 99%

Glycan susceptibility factors in autism spectrum disorders

Dwyer

2016

Molecular Aspects of Medicine

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“…Although α-dystroglycan (α-DG) is well known to be modified with O-mannose glycans, it is a minor among O-mannosylated proteins in the mammalian brain [114]. Instead, other glycoproteins, including PTPRZ (or its secreted form called phosphacan), CD24, mainly carry O-mannose glycans, and glycomic analyses have shown that their O-mannose glycans have a β1,6-GlcNAc branch generated by GnT-IX [115][116][117]. Mgat5b-deficient mice lack most of branched O-mannose glycans in their brain [118], and additional knockout of Mgat5 leads to complete loss of this branch, indicating that β1,6-GlcNAc branching of O-mannose glycans is mediated dominantly by GnT-IX and only marginally by GnT-V. Functionally, GnT-IX-producing glycans are involved in recovery of myelin damage [119].…”

Section: Functional Overview Of Gnt-ix (Gnt-vb)mentioning

confidence: 99%

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

Nagae

Yamaguchi

Taniguchi

et al. 2020

IJMS

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Glycosylation is the most ubiquitous post-translational modification in eukaryotes. N-glycan is attached to nascent glycoproteins and is processed and matured by various glycosidases and glycosyltransferases during protein transport. Genetic and biochemical studies have demonstrated that alternations of the N-glycan structure play crucial roles in various physiological and pathological events including progression of cancer, diabetes, and Alzheimer’s disease. In particular, the formation of N-glycan branches regulates the functions of target glycoprotein, which are catalyzed by specific N-acetylglucosaminyltransferases (GnTs) such as GnT-III, GnT-IVs, GnT-V, and GnT-IX, and a fucosyltransferase, FUT8s. Although the 3D structures of all enzymes have not been solved to date, recent progress in structural analysis of these glycosyltransferases has provided insights into substrate recognition and catalytic reaction mechanisms. In this review, we discuss the biological significance and structure-function relationships of these enzymes.

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“…RPTP is expressed in 3 alternatively spliced forms RPTP-, RPTP- , and a truncated form of RPTP- with an 860 amino acid deletion (Fig 3c). Phosphacan is the proteolytically released ecto-domain of the transmembrane protein tyrosine phosphatase receptor- of neurons and glial cells [75] and is a principal CNS proteoglycan promoting neuron-glial interactions, neuronal differentiation, myelination and axonal repair. The transient nature of cell signalling by phosphorylation requires specific phosphatases for regulatory control.…”

Section: Phosphacanmentioning

confidence: 99%

Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

Hayes

Sugahara

Farrugia

et al. 2018

Biochemical Journal

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Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, CS PGs play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here, we review (i) the biodiversity of CS PGs and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair.

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Neurons and Glia Modify Receptor Protein-tyrosine Phosphatase ζ (RPTPζ)/Phosphacan with Cell-specific O-Mannosyl Glycans in the Developing Brain

Cited by 33 publications

References 64 publications

Glycan susceptibility factors in autism spectrum disorders

Glycan susceptibility factors in autism spectrum disorders

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

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