Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons

Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons
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DOI:
10.1016/j.neures.2010.02.008
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发表时间:
2010-06-01
影响因子:
2.9
通讯作者:
Sakagami, Hiroyuki
Sakagami, Hiroyuki
中科院分区:
医学4区
文献类型:
--
作者:
Sanda, Masashi;Ohara, Naoki;Sakagami, Hiroyuki

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ADP-核糖基化因子6(ARF 6)是一种小的GT3,可能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、树突和棘的形成。在试图确定的分子机制,调节神经元形态发生的ARF 6,我们确定了vezatin作为一种新的结合伙伴的活性GTP结合的ARF 6酵母双杂交筛选。Vezatin能够特异性结合ARF家族中的GTP-ARF 6。在成年小鼠脑中,vezatin表现出广泛的基因表达,在海马和内侧缰核中具有高水平。在海马神经元中,vezatin定位于树突以及细胞体。敲低内源性vezatin显着减少总树突长度和培养的海马神经元的树枝状,而过度表达vezatin增加树突长度。我们目前的研究表明,vezatin可能调节树突状细胞的形成作为下游效应的ARF 6。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
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. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.