Abstract
Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABA(A) receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Dentate Gyrus / cytology
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Dentate Gyrus / metabolism*
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Female
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Gene Knockdown Techniques
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HeLa Cells
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism*
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Rats
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Rats, Sprague-Dawley
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Receptor, Fibroblast Growth Factor, Type 1 / genetics
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Receptor, Fibroblast Growth Factor, Type 1 / metabolism
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Receptors, GABA-A / genetics
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Receptors, GABA-A / metabolism*
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Signal Transduction / physiology*
Substances
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Carrier Proteins
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Cell Adhesion Molecules
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Membrane Proteins
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Nerve Growth Factors
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Nfasc protein, rat
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Receptors, GABA-A
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gephyrin
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Fgfr1 protein, rat
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Receptor, Fibroblast Growth Factor, Type 1