Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea.
Eur J Neurosci. 2012 Jul;36(1):1960-70. doi: 10.1111/j.1460-9568.2012.08124.x. Epub 2012 May 17.
In neuronal development, dendritic outgrowth and arborization are important for the establishment of neural circuit formation. A previous study reported that PSD-95-interacting regulator of spine morphogenesis (Preso) formed a complex with PAK-interacting exchange factor-beta (βPix) via PSD-95/Dlg/ZO-1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant-negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F-actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5-bisphosphate (PIP(2) ) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP(2) and it did not rescue the Preso-knockdown effect. These results indicate that PIP(2) is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix.
在神经元发育过程中，树突的生长和分支对于神经网络的形成至关重要。之前的研究表明，PSD-95 相互作用的树突形态发生调节因子（Preso）通过 PSD-95/Dlg/ZO-1（PDZ）相互作用与 PAK 相互作用的交换因子-β（βPix）形成复合物。在这里，我们报告 Preso 及其结合蛋白βPix 定位于树突生长锥。在培养的神经元中敲低和显性负性抑制 Preso 显著减少了树突的生长，但不影响分支，并且导致神经元树突尖端的βPix 和 F-肌动蛋白的强度降低。此外，磷脂酰肌醇 4,5-二磷酸（PIP2）诱导 Preso 向开放 PDZ 结构域的构象变化，并增强与βPix 的相互作用。此外，Preso 带 4.1 蛋白、埃兹蛋白、radixin 和膜突蛋白（FERM）结构域突变体不能与 PIP2 相互作用，也不能挽救 Preso 敲低的效果。这些结果表明，PIP2 是一种关键的信号分子，通过 Preso 和βPix 之间的相互作用激活小 GTPase 信号，从而调节树突的生长。
