ArticleCellular and molecular life sciences : CMLS2012
Homeostatic regulation of NCAM polysialylation is critical for correct synaptic targeting.
Article in Cellular and molecular life sciences : CMLS, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Salmonid polysialyltransferases to generate a variety of sialic acid polymers.Scientific reports · 2023Article
- Time and space-resolved quantification of plasma membrane sialylation for measurements of cell function and neurotoxicity.Archives of toxicology · 2020Article
- Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders.Molecular psychiatry · 2018Article
- Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration.Biomaterials science · 2018Review
- Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines.Journal of visualized experiments : JoVE · 2017Article
- Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- Review
- Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling.Neuron · 2016Article
- Genealogical correspondence of a forebrain centre implies an executive brain in the protostome-deuterostome bilaterian ancestor.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Article
- In vivo stimulation of early peripheral axon regeneration by N-propionylmannosamine in the presence of polysialyltransferase ST8SIA2.Journal of neural transmission (Vienna, Austria : 1996) · 2015Article
- N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury.Neural regeneration research · 2015Article
- Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration.Physiological reviews · 2014Review
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19 authors.
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Abstract
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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