Abstract
Vezatin is an integral membrane protein associated with cell-cell adhesion complex and actin cytoskeleton. It is expressed in the developing and mature mammalian brain, but its neuronal function is unknown. Here, we show that Vezatin localizes in spines in mature mouse hippocampal neurons and codistributes with PSD95, a major scaffolding protein of the excitatory postsynaptic density. Forebrain-specific conditional ablation of Vezatin induced anxiety-like behavior and impaired cued fear-conditioning memory response. Vezatin knock-down in cultured hippocampal neurons and Vezatin conditional knock-out in mice led to a significantly increased proportion of stubby spines and a reduced proportion of mature dendritic spines. PSD95 remained tethered to presynaptic terminals in Vezatin-deficient hippocampal neurons, suggesting that the reduced expression of Vezatin does not compromise the maintenance of synaptic connections. Accordingly, neither the amplitude nor the frequency of miniature EPSCs was affected in Vezatin-deficient hippocampal neurons. However, the AMPA/NMDA ratio of evoked EPSCs was reduced, suggesting impaired functional maturation of excitatory synapses. These results suggest a role of Vezatin in dendritic spine morphogenesis and functional synaptic maturation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Anxiety / genetics
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Avoidance Learning / physiology
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Cadherins / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Conditioning, Psychological / physiology
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Dendritic Spines / physiology*
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Electric Stimulation
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Embryo, Mammalian
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Excitatory Postsynaptic Potentials / genetics
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Excitatory Postsynaptic Potentials / physiology*
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Exploratory Behavior / physiology
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Eye Proteins / genetics
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Fear / physiology
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Gene Expression Regulation / genetics
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Glutamate Decarboxylase / metabolism
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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In Vitro Techniques
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Male
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Maze Learning / physiology
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Membrane Proteins / deficiency
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Membrane Proteins / metabolism*
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Memory / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Confocal
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Microtubule-Associated Proteins / metabolism
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N-Methylaspartate / metabolism
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Nerve Tissue Proteins / metabolism
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Neurogenesis / genetics
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Neurogenesis / physiology*
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Neurons / ultrastructure*
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RNA, Messenger
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism
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Silver Staining
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Statistics, Nonparametric
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Synapses / genetics
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Synapses / physiology*
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Synaptosomes / metabolism
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Transfection
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Vesicle-Associated Membrane Protein 2 / metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
Substances
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Cadherins
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Carrier Proteins
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Dach1 protein, mouse
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Eye Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, AMPA
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Vesicle-Associated Membrane Protein 2
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vezatin protein, mouse
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Green Fluorescent Proteins
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N-Methylaspartate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Glutamate Decarboxylase
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glutamate decarboxylase 1
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glutamate receptor ionotropic, AMPA 2