Abstract
Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) - a molecule essential for long-term potentiation of synaptic strength - upregulated and recruited copine-6 to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased mushroom spine number and decreased filopodia number, while copine-6 knockdown had the opposite effect and dramatically increased the number of filopodia, which lacked PSD95. Functionally, manipulation of post-synaptic copine-6 levels affected miniature excitatory post-synaptic current (mEPSC) kinetics and evoked synaptic vesicle recycling in contacting boutons, and post-synaptic knockdown of copine-6 reduced hippocampal LTP and increased LTD. Mechanistically, copine-6 promotes BDNF-TrkB signaling and recycling of activated TrkB receptors back to the plasma membrane surface, and is necessary for BDNF-induced increases in mushroom spines in hippocampal neurons. Thus copine-6 regulates BDNF-dependent changes in dendritic spine morphology to promote synaptic plasticity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / pharmacology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Dendritic Spines / physiology*
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Dendritic Spines / ultrastructure
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Disks Large Homolog 4 Protein / metabolism
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Hippocampus / cytology*
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Humans
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Mice
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Microtubule-Associated Proteins / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / physiology*
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Neurons / ultrastructure*
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Organ Culture Techniques
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Rats
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Receptor, trkB / genetics
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Receptor, trkB / metabolism
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Synapses / drug effects
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Synapses / physiology
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Synapses / ultrastructure
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Synaptic Potentials / drug effects
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Synaptic Potentials / genetics
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Synaptic Vesicles / drug effects
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Synaptic Vesicles / physiology*
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Synaptosomes / metabolism
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Synaptosomes / ultrastructure
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Vesicular Glutamate Transport Protein 1 / metabolism
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Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
Substances
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Brain-Derived Neurotrophic Factor
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CPNE6 protein, rat
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Carrier Proteins
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Disks Large Homolog 4 Protein
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MAP2 protein, rat
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Slc32a1 protein, rat
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Vesicular Glutamate Transport Protein 1
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Vesicular Inhibitory Amino Acid Transport Proteins
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Ntrk2 protein, rat
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Receptor, trkB