Abstract
Synaptic cell adhesion molecules (CAMs) regulate synapse formation through their trans-synaptic and heterophilic adhesion. Here we show that postsynaptic netrin-G ligand (NGL) CAMs associate with netrin-G CAMs in an isoform-specific manner and, through their cytosolic tail, with the abundant postsynaptic scaffold postsynaptic density-95 (PSD-95). Overexpression of NGL-2 in cultured rat neurons increased the number of PSD-95-positive dendritic protrusions. NGL-2 located on heterologous cells or beads induced functional presynaptic differentiation in contacting neurites. Direct aggregation of NGL-2 on the surface membrane of dendrites induced the clustering of excitatory postsynaptic proteins. Competitive inhibition by soluble NGL-2 reduced the number of excitatory synapses. NGL-2 knockdown reduced excitatory, but not inhibitory, synapse numbers and currents. These results suggest that NGL regulates the formation of excitatory synapses.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / pharmacology
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Cell Adhesion Molecules / metabolism*
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Cell Differentiation / genetics
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Cells, Cultured
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Coculture Techniques
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Dendrites / metabolism
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Dendrites / ultrastructure
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Embryo, Mammalian
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Fluorescent Antibody Technique / methods
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Membrane Proteins / pharmacology
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Mice
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Microscopy, Immunoelectron / methods
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Mutagenesis / physiology
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Netrins
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Neurons / cytology*
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Neurons / ultrastructure
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Patch-Clamp Techniques / methods
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RNA, Small Interfering / pharmacology
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Receptors, Cell Surface / physiology*
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Synapses / diagnostic imaging
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Synapses / drug effects
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Synapses / physiology*
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Synaptophysin / metabolism
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Transfection / methods
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Ultrasonography
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Vesicular Glutamate Transport Protein 1 / metabolism
Substances
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Carrier Proteins
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Cell Adhesion Molecules
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Intracellular Signaling Peptides and Proteins
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LRRC4C protein, human
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Membrane Proteins
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Nerve Tissue Proteins
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Netrins
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RNA, Small Interfering
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Receptors, Cell Surface
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Synaptophysin
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Vesicular Glutamate Transport Protein 1
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gephyrin
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netrin-G1
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Green Fluorescent Proteins