Department of Anatomy, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara 228-8555, Kanagawa, Japan.
Neurosci Res. 2010 Jun;67(2):126-36. doi: 10.1016/j.neures.2010.02.008. Epub 2010 Feb 24.
ADP-ribosylation factor 6 (ARF6) is a small GTPase that regulates neuronal morphogenesis processes such as axonal, dendritic, and spine formation possibly through the actin cytoskeleton and membrane trafficking. In an attempt to define the molecular mechanisms that regulate neuronal morphogenesis by ARF6, we identified vezatin as a novel binding partner of active GTP-bound ARF6 using yeast two-hybrid screening. Vezatin was able to bind specifically to GTP-ARF6 among the ARF family. In the adult mouse brain, vezatin exhibited widespread gene expression with high levels in the hippocampus and medial habenular nucleus. In hippocampal neurons, vezatin was localized at dendrites as well as cell bodies. Knockdown of endogenous vezatin significantly reduced total dendritic length and arborization of cultured hippocampal neurons, while overexpression of vezatin increased dendritic length. Our present study suggests that vezatin may regulate dendritic formation as a downstream effector of ARF6.
ADP-核糖基化因子 6(ARF6)是一种小分子 GTPase,通过肌动蛋白细胞骨架和膜运输,调节神经元形态发生过程,如轴突、树突和棘形成。为了确定 ARF6 调节神经元形态发生的分子机制,我们使用酵母双杂交筛选鉴定了 vezatin 是活性 GTP 结合的 ARF6 的新结合伴侣。Vezatin 能够在 ARF 家族中特异性结合 GTP-ARF6。在成年小鼠大脑中,vezatin 表现出广泛的基因表达,在海马体和中脑核中有高水平表达。在海马神经元中,vezatin 定位于树突和细胞体。内源性 vezatin 的敲低显著减少了培养的海马神经元的总树突长度和分支,而过表达 vezatin 则增加了树突长度。我们的研究表明,vezatin 可能作为 ARF6 的下游效应物调节树突形成。