Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Büttner, Bettina; Kannicht, Christoph; Schmidt, Carolin; Löster, Klemens; Reutter, Werner; Lee, Hye-Youn; Nöhring, Sabine; Horstkorte, Rüdiger

doi:10.1523/jneurosci.22-20-08869.2002

Cited by 56 publications

(44 citation statements)

References 36 publications

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“…Similar results were obtained with primary neurones [20]. In brain slices we could show that the re-establishment of the perforant pathway was stimulated when the slices were cultured in the presence of ManNProp or ManNAc [20].…”

Section: Introductionsupporting

confidence: 86%

Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells

et al. 2008

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Sialic acid precursors are mediators of the sialic acid pathway. In this manuscript we present evidence that the application of sialic acid a precursor modulates gene expression and cell differentiation. The concept that sugars are involved in cellular transcription was first proposed by Jacob and Monod nearly 40 years ago studying the regulation of the lac-operon in prokaryotes. Surprisingly, these findings have never been transferred to eukaryotic systems. For our studies we have chosen PC12 cells. PC12-cells differentiate after application of NGF into a neuron-like phenotype. It is shown that treatment of PC12 cells with two different sialic acid precursors N-acetyl- or N-propanoylmannosamine, without application of NGF also induces neurite outgrowth. Moreover, the PC12 cells show the same morphology as the NGF-treated cells. Surprisingly, after application of both sialic acid precursors the phosphorylation and translocation of erk1/2 into the nucleus are activated, thus influencing the expression of genes involved in the differentiation of cells, such as the transcription factor c-Jun or TOAD-64/Ulip/CRMP (Turned ON After Division, 64 kd/ unc-33-like phosphoprotein/Collapsin Response Mediator Protein). These are the first experimental data showing that the sialic acid metabolism is closely associated with signal transduction and regulation of neuronal differentiation.

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Section: Introductionsupporting

confidence: 86%

Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells

et al. 2008

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“…This data is further corroborated by downstream analysis of ManNProp, which revealed downregulation of the 14-3-3e protein [49], which is encoded by a recently identified susceptibility gene for schizophrenia (YWHAE) [50], and is a downstream target of DISC-1 [51].…”

Section: Discussionmentioning

confidence: 53%

Homeostatic regulation of NCAM polysialylation is critical for correct synaptic targeting

Vogt

Glumm

Schlüter

et al. 2011

Cell. Mol. Life Sci.

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During development, axonal projections have a remarkable ability to innervate correct dendritic subcompartments of their target neurons and to form regular neuronal circuits. Altered axonal targeting with formation of synapses on inappropriate neurons may result in neurodevelopmental sequelae, leading to psychiatric disorders. Here we show that altering the expression level of the polysialic acid moiety, which is a developmentally regulated, posttranslational modification of the neural cell adhesion molecule NCAM, critically affects correct circuit formation. Using a chemically modified sialic acid precursor (N-propyl-D: -mannosamine), we inhibited the polysialyltransferase ST8SiaII, the principal enzyme involved in polysialylation during development, at selected developmental time-points. This treatment altered NCAM polysialylation while NCAM expression was not affected. Altered polysialylation resulted in an aberrant mossy fiber projection that formed glutamatergic terminals on pyramidal neurons of the CA1 region in organotypic slice cultures and in vivo. Electrophysiological recordings revealed that the ectopic terminals on CA1 pyramids were functional and displayed characteristics of mossy fiber synapses. Moreover, ultrastructural examination indicated a "mossy fiber synapse"-like morphology. We thus conclude that homeostatic regulation of the amount of synthesized polysialic acid at specific developmental stages is essential for correct synaptic targeting and circuit formation during hippocampal development.

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“…We used this method to describe, for the first time to our knowledge, the real-time distribution of polysialic acids on the membranes of neurons. cerebellar cells (11,12). On the other hand, Bertozzi and coworkers (19)(20)(21)(22) metabolically introduced monosaccharidebased chemical reporters-N-acyl derivatives of ManNAc, N-acetyl-D-glucosamine, or N-acetyl-D-galactosamine containing a ketone or azide group-onto cellular surface glycans followed by bioorthogonal, chemoselective coupling with a fluorescent dye or an affinity tag bearing hydrazide/aminooxy (for ketones) or phosphine/alkyne (for azides) group.…”

Section: Significancementioning

confidence: 99%

“…PSA-NCAMs occasionally remain until adulthood in the brain regions that exhibit plasticity, including hippocampus, and they are reported to be involved in glia-neuron interactions, regulation of circadian rhythms, and learning and memory (10). Other than these roles, PSA is closely related to the tumor progression of malignant neuroblastoma (11,12). However, despite the widespread occurrence of PSAs and their biological complexity in the nerve systems, the PSA-mediated modulation of neuronal functions is not fully understood.…”

mentioning

confidence: 99%

Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons

Kang

Joo

Choi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The posttranslational modification of neural cell-adhesion molecule (NCAM) with polysialic acid (PSA) and the spatiotemporal distribution of PSA-NCAM play an important role in the neuronal development. In this work, we developed a tissue-based strategy for metabolically incorporating an unnatural monosaccharide, peracetylated N-azidoacetyl-D-mannosamine, in the sialic acid biochemical pathway to present N-azidoacetyl sialic acid to PSA-NCAM. Although significant neurotoxicity was observed in the conventional metabolic labeling that used the dissociated neuron cells, neurotoxicity disappeared in this modified strategy, allowing for investigation of the temporal and spatial distributions of PSA in the primary hippocampal neurons. PSA-NCAM was synthesized and recycled continuously during neuronal development, and the two-color labeling showed that newly synthesized PSANCAMs were transported and inserted mainly to the growing neurites and not significantly to the cell body. This report suggests a reliable and cytocompatible method for in vitro analysis of glycans complementary to the conventional cell-based metabolic labeling for chemical glycobiology.

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Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Cited by 56 publications

References 36 publications

Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells

Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells

Homeostatic regulation of NCAM polysialylation is critical for correct synaptic targeting

Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons

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