title: Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.
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.
authors: Centre National de la Recherche Scientifique-CNRS UMR7592, Université Paris Diderot, Sorbonne Paris Cité, Institut Jacques Monod, 75205 Paris, France.
authors: Lydia
authors: L
authors: Danglot
authors: Thomas
authors: T
authors: Freret
authors: Nicolas
authors: N
authors: Le Roux
authors: Nicolas
authors: N
authors: Narboux Nême
authors: Andrea
authors: A
authors: Burgo
authors: Vincent
authors: V
authors: Hyenne
authors: Anne
authors: A
authors: Roumier
authors: Vincent
authors: V
authors: Contremoulins
authors: François
authors: F
authors: Dauphin
authors: Jean-Charles
authors: JC
authors: Bizot
authors: Guilan
authors: G
authors: Vodjdani
authors: Patricia
authors: P
authors: Gaspar
authors: Michel
authors: M
authors: Boulouard
authors: Jean-Christophe
authors: JC
authors: Poncer
authors: Thierry
authors: T
authors: Galli
authors: Marie-Christine
authors: MC
authors: Simmler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000235:genetics; D001362:Avoidance Learning / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics; D005239:Fear / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000648:ultrastructure*; D012333:RNA, Messenger; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D016622:Silver Staining; D018709:Statistics, Nonparametric; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; C456264:Dach1 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018091:Receptors, AMPA; D050988:Vesicle-Associated Membrane Protein 2; C506603:vezatin protein, mouse; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C104722:glutamate receptor ionotropic, AMPA 2