Spikar, a novel drebrin‐binding protein, regulates the formation and stabilization of dendritic spines
Spikar, a novel drebrin‐binding protein, regulates the formation and stabilization of dendritic spines
复制标题
DOI：
10.1111/jnc.12486
复制
发表时间：
2014-02
影响因子：
4.7
通讯作者：
H. Yamazaki;N. Kojima;Kenichi Kato;E. Hirose;T. Iwasaki;T. Mizui;Hideto Takahashi;K. Hanamura;R. T. Roppongi;N. Koibuchi;Y. Sekino;N. Mori;T. Shirao
中科院分区：
文献类型：
--
作者：
H. Yamazaki;N. Kojima;Kenichi Kato;E. Hirose;T. Iwasaki;T. Mizui;Hideto Takahashi;K. Hanamura;R. T. Roppongi;N. Koibuchi;Y. Sekino;N. Mori;T. Shirao
树突棘是树突上小的、富含肌动蛋白的突起，其发育是神经回路形成的基础。肌动蛋白细胞骨架是树突棘形态发生的中心。dreplastin是一种肌动蛋白结合蛋白，被认为通过突触后位点的独特dreplastin-肌动蛋白复合物启动棘形成。然而，神经元中的drexin过表达并不增加树突棘的最终密度。在这项研究中，我们已经确定并表征了一种新的dreplasm结合蛋白，spikar。Spikar定位于细胞核和树突棘中，并且Spikar在树突棘中的积累与棘密度直接相关。一项报告基因测定表明，spikar可作为核受体的转录共激活因子。我们发现，树突棘，而不是核，定位spikar需要drepletion。RNA干扰敲低和过表达实验表明，单核spikar通过调节从头棘形成和现有棘的缩回来调节树突棘密度。与树突棘不同，spikar不影响树突棘的形态或功能。这些发现表明，dreplatin介导的spikar的突触后积累调节棘密度，但不参与棘形态的调节。
Dendritic spines are small, actin‐rich protrusions on dendrites, the development of which is fundamental for the formation of neural circuits. The actin cytoskeleton is central to dendritic spine morphogenesis. Drebrin is an actin‐binding protein that is thought to initiate spine formation through a unique drebrin‐actin complex at postsynaptic sites. However drebrin overexpression in neurons does not increase the final density of dendritic spines. In this study, we have identified and characterized a novel drebrin‐binding protein, spikar. Spikar is localized in cell nuclei and dendritic spines, and accumulation of spikar in dendritic spines directly correlates with spine density. A reporter gene assay demonstrated that spikar acts as a transcriptional co‐activator for nuclear receptors. We found that dendritic spine, but not nuclear, localization of spikar requires drebrin. RNA‐interference knockdown and overexpression experiments demonstrated that extranuclear spikar regulates dendritic spine density by modulating de novo spine formation and retraction of existing spines. Unlike drebrin, spikar does not affect either the morphology or function of dendritic spines. These findings indicate that drebrin‐mediated postsynaptic accumulation of spikar regulates spine density, but is not involved in regulation of spine morphology.