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RESEARCH PRODUCT
Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.
Eva BenitoJeffrey McilhinneyHamid AhmadSaheeb AhmedJoaquin I. Hurtado-zavalaBinu RamachandranPavel V PerestenkoKatja BurkAarti SwaminathanCamin DeanAnkit AwasthiRuth FaramAndre Fischersubject
0301 basic medicineDendritic spineVesicular Inhibitory Amino Acid Transport Proteinsdrug effects [Synapses]Tropomyosin receptor kinase BHippocampal formationgenetics [Carrier Proteins]pharmacology [Brain-Derived Neurotrophic Factor]Hippocampusmetabolism [Vesicular Inhibitory Amino Acid Transport Proteins]Mtap2 protein ratMice0302 clinical medicineNeurotrophic factorsdrug effects [Synaptic Vesicles]genetics [Nerve Tissue Proteins]Cells Culturedultrastructure [Neurons]NeuronsChemistryLong-term potentiationSynaptic Potentialsphysiology [Neurons]physiology [Dendritic Spines]Cell biologyultrastructure [Dendritic Spines]metabolism [Receptor trkB]Synaptic VesiclesFilopodiaultrastructure [Synaptosomes]Disks Large Homolog 4 ProteinMicrotubule-Associated ProteinsCognitive NeuroscienceDendritic Spinesmetabolism [Disks Large Homolog 4 Protein]Nerve Tissue Proteinsgenetics [Receptor trkB]03 medical and health sciencesCellular and Molecular NeuroscienceOrgan Culture Techniquesphysiology [Synaptic Vesicles]metabolism [Vesicular Glutamate Transport Protein 1]TrkB protein ratdrug effects [Synaptic Potentials]Synaptic vesicle recyclingAnimalsHumansReceptor trkBddc:610metabolism [Synaptosomes]metabolism [Nerve Tissue Proteins]Viaat protein ratBrain-Derived Neurotrophic Factormetabolism [Microtubule-Associated Proteins]Rats030104 developmental biologygenetics [Synaptic Potentials]nervous systemcytology [Hippocampus]Synaptic plasticityultrastructure [Synapses]SynapsesVesicular Glutamate Transport Protein 1CPNE6 protein ratphysiology [Synapses]Carrier Proteins030217 neurology & neurosurgerymetabolism [Carrier Proteins]Synaptosomesdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-13 | Cerebral cortex (New York, N.Y. : 1991) |