Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons
| Autor: | Vishwa Mohan, Ingo Gotthard, Patricia F. Maness, Chelsea S. Sullivan, Elliott V. Wyatt, Richard J. Weinberg, Srihita Bongu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptor complex Interneuron lcsh:Medicine Article Synapse 03 medical and health sciences Mice 0302 clinical medicine Neurocan Interneurons medicine Animals Humans Protein Interaction Domains and Motifs GABAergic Neurons lcsh:Science Neural Cell Adhesion Molecules Cerebral Cortex Multidisciplinary Chemistry Perineuronal net lcsh:R Receptor EphA3 Receptor Protein-Tyrosine Kinases 030104 developmental biology medicine.anatomical_structure nervous system Synaptic plasticity GABAergic Neural cell adhesion molecule lcsh:Q Neuroscience 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Perineuronal nets (PNNs) are implicated in closure of critical periods of synaptic plasticity in the brain, but the molecular mechanisms by which PNNs regulate synapse development are obscure. A receptor complex of NCAM and EphA3 mediates postnatal remodeling of inhibitory perisomatic synapses of GABAergic interneurons onto pyramidal cells in the mouse frontal cortex necessary for excitatory/inhibitory balance. Here it is shown that enzymatic removal of PNN glycosaminoglycan chains decreased the density of GABAergic perisomatic synapses in mouse organotypic cortical slice cultures. Neurocan, a key component of PNNs, was expressed in postnatal frontal cortex in apposition to perisomatic synapses of parvalbumin-positive interneurons. Polysialylated NCAM (PSA-NCAM), which is required for ephrin-dependent synapse remodeling, bound less efficiently to neurocan than mature, non-PSA-NCAM. Neurocan bound the non-polysialylated form of NCAM at the EphA3 binding site within the immunoglobulin-2 domain. Neurocan inhibited NCAM/EphA3 association, membrane clustering of NCAM/EphA3 in cortical interneuron axons, EphA3 kinase activation, and ephrin-A5-induced growth cone collapse. These studies delineate a novel mechanism wherein neurocan inhibits NCAM/EphA3 signaling and axonal repulsion, which may terminate postnatal remodeling of interneuron axons to stabilize perisomatic synapses in vivo. |
| Databáze: | OpenAIRE |
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