Abstract
Vilse/Arhgap39 is a Rho GTPase activating protein (RhoGAP) and utilizes its WW domain to regulate Rac/Cdc42-dependent morphogenesis in Drosophila and murine hippocampal neurons. However, the function of Vilse in mammalian dendrite architecture and synaptic plasticity remained unclear. In the present study, we aimed to explore the possible role of Vilse in dendritic structure and synaptic function in the brain. Homozygous knockout of Vilse resulted in premature embryonic lethality in mice. Changes in dendritic complexity and spine density were noticed in hippocampal neurons of Camk2a-Cre mediated forebrain-specific Vilse knockout (VilseΔ/Δ) mice. VilseΔ/Δ mice displayed impaired spatial memory in water maze and Y-maze tests. Electrical stimulation in hippocampal CA1 region revealed that the synaptic transmission and plasticity were defected in VilseΔ/Δ mice. Collectively, our results demonstrate that Vilse is essential for embryonic development and required for spatial memory.
Highlights
Most excitatory synapses in the mammalian brain locate at dendritic spines and the formation and dynamics of dendritic spines are mainly determined by the actin cytoskeleton[4]
To address the function of Vilse in vivo, embryonic stem (ES) cells with LacZ reporter insertion in Vilse allele were obtained from International Mouse Phenotyping Consortium (IMPC)
Camk2a-mediated Vilse ablation in mice did not result in premature embryonic death, suggesting that Vilse might not be essential for cell viability in neuronal cells
Summary
Most excitatory synapses in the mammalian brain locate at dendritic spines and the formation and dynamics of dendritic spines are mainly determined by the actin cytoskeleton[4]. Rho GTPases play important roles in the morphogenesis of dendritic spines and synaptic plasticity by modulating the actin organization[5,6,7,8]. Elimination of Rac[1] in excitatory neurons in the forebrain in vivo affects spine structure and impairs synaptic plasticity in the hippocampus with defects in spatial learning[13]. Mutants claim that Vilse transduces signals downstream of Robo receptor to regulate Rac-dependent midline repulsion in Drosophila[15,16]. Vilse interacts with connector enhancer of KSR-2 (CNK2) in the postsynaptic membrane via WW domain to modulate Rac/Cdc[42] signaling during spine morphogenesis in hippocampal neurons[17]. In VilseΔ/Δ mice, the dendritic architecture in the hippocampal neurons were altered while hippocampus-mediated spatial learning/memory function was impaired. Our results led to a conclusion that Vilse is essential for embryonic development and required for dendritic structure and synaptic function
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