Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.

Lydia Danglot (1, 2) , Thomas Freret (3) , Nicolas Le Roux (4) , Nicolas Narboux Nême (4) , Andrea Burgo (1, 2) , Vincent Hyenne (5) , Anne Roumier (4) , Vincent Contremoulins (1) , François Dauphin (3) , Jean-Charles Bizot (6) , Guilan Vodjdani (7) , Patricia Gaspar (4) , Michel Boulouard (3) , Jean-Christophe Poncer (8) , Thierry Galli (1, 2) , Marie-Christine Simmler (1, 2)

1 IJM (UMR_7592) - Institut Jacques Monod
2 INSERM ERL U950, Membrane Traffic in Neuronal and Epithelial Morphogenesis
3 GMPc - Groupe Mémoire et Plasticité comportementale
4 Institut du Fer à Moulin
5 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
6 Key-Obs
7 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
8 Cortex et Epilepsie [Paris]

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.

Domaines: Neurosciences [q-bio.NC]

Lydia Danglot, Thomas Freret, Nicolas Le Roux, Nicolas Narboux Nême, Andrea Burgo, et al.. Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.. Journal of Neuroscience, 2012, 32 (26), pp.9007-22. ⟨10.1523/JNEUROSCI.3084-11.2012⟩. ⟨hal-00776396⟩