PLD1 Negatively Regulates Dendritic Branching

PLD1 Negatively Regulates Dendritic Branching
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PLD1 负调控树突分支

DOI:
10.1523/jneurosci.5378-11.2012
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发表时间:
2012-06
影响因子:
5.3
通讯作者:
Wang, Yun
Wang, Yun
中科院分区:
医学1区
文献类型:
--
作者:
Qi, Cai;Li, Gang;Yin, Dong-Min;Wang, Yun

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神经元具有有助于信息处理的特征性树突状分支模式。树突树枝化的一个重要组成部分是形成特定数量的分支。虽然促进树突生长和分支的细胞内途径正在阐明,负调控树突分支的机制仍然是谜。在这项研究中,使用获得的功能和功能丧失的研究,我们表明,磷脂酶D1(PLD 1)作为一个负调节器的树突状分支在培养的海马神经元从胚胎第18天的大鼠胚胎。野生型PLD 1(WT-PLD 1)的过表达降低树突的复杂性,而敲低或抑制PLD 1增加树突分支。我们进一步证明了PLD 1作用于RhoA(一种小Rho GTP酶)下游,以抑制树突状分支。组成型活性RhoA(V14-RhoA)对树突状分支的限制可以通过敲低PLD 1来部分地挽救。此外,V14-RhoA和WT-PLD 1对树突状分支的抑制可以通过降低磷脂酸(PA)的水平而部分改善,磷脂酸是PLD 1的酶促产物。总之,这些结果表明,RhoA-PLD 1-PA可能代表了一种新的信号通路的限制树突状分支,从而可能提供深入了解树突状形态发生的机制。
Neurons have characteristic dendritic arborization patterns that contribute to information processing. One essential component of dendritic arborization is the formation of a specific number of branches. Although intracellular pathways promoting dendritic growth and branching are being elucidated, the mechanisms that negatively regulate the branching of dendrites remain enigmatic. In this study, using gain-of-function and loss-of-function studies, we show that phospholipase D1 (PLD1) acts as a negative regulator of dendritic branching in cultured hippocampal neurons from embryonic day 18 rat embryos. Overexpression of wild-type PLD1 (WT-PLD1) decreases the complexity of dendrites, whereas knockdown or inhibition of PLD1 increases dendritic branching. We further demonstrated that PLD1 acts downstream of RhoA, one of the small Rho GTPases, to suppress dendritic branching. The restriction of dendritic branching by constitutively active RhoA (V14-RhoA) can be partially rescued by knockdown of PLD1. Moreover, the inhibition of dendritic branching by V14-RhoA and WT-PLD1 can be partially ameliorated by reducing the level of phosphatidic acid (PA), which is the enzymatic product of PLD1. Together, these results suggest that RhoA-PLD1-PA may represent a novel signaling pathway in the restriction of dendritic branching and may thus provide insight into the mechanisms of dendritic morphogenesis.
缺乏磷脂酶D1的小鼠中的α(IIB)β(3)整联蛋白活化和剪切依赖性血栓形成。
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