Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Sialylation is essential for development and regeneration in mammals. Using N-propanoylmannosamine, a novel precursor of sialic acid, we were able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into cell surface glycoconjugates. Here we re...

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Bibliographic Details
Published in:The Journal of neuroscience 2002-10, Vol.22 (20), p.8869-8875
Main Authors: Buttner, Bettina, Kannicht, Christoph, Schmidt, Carolin, Loster, Klemens, Reutter, Werner, Lee, Hye-Youn, Nohring, Sabine, Horstkorte, Rudiger
Format: Article
Language:English
Subjects:
Animals
Axons - drug effects
Axons - physiology
Cell Differentiation - drug effects
Cell Membrane - chemistry
Cell Membrane - metabolism
Cells, Cultured
Cerebellum - cytology
Electrophoresis, Gel, Two-Dimensional
Female
Hexosamines - metabolism
Hexosamines - pharmacology
Male
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred BALB C
Nerve Regeneration - drug effects
Nerve Regeneration - physiology
Neuraminic Acids - metabolism
Neuraminic Acids - pharmacology
Neurites - drug effects
Neurites - physiology
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
PC12 Cells
Perforant Pathway - cytology
Perforant Pathway - drug effects
Proteome - analysis
Rats
Sialic Acids - chemistry
Sialic Acids - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Summary:Sialylation is essential for development and regeneration in mammals. Using N-propanoylmannosamine, a novel precursor of sialic acid, we were able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into cell surface glycoconjugates. Here we report that this biochemical engineering of sialic acid leads to a stimulation of neuronal cells. Both PC12 cells and cerebellar neurons showed a significant increase in neurite outgrowth after treatment with this novel sialic acid precursor. Furthermore, also the reestablishment of the perforant pathway was stimulated in brain slices. In addition, we surprisingly identified several cytosolic proteins with regulatory functions, which are differentially expressed after treatment with N-propanoylmannosamine. Because sialic acid is the only monosaccharide that is activated in the nucleus, we hypothesize that transcription could be modulated by the unnatural CMP-N-propanoylneuraminic acid and that sialic acid activation might be a general tool to regulate cellular functions, such as neurite outgrowth.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.22-20-08869.2002