NESH Regulates Dendritic Spine Morphology and Synapse Formation
NESH Regulates Dendritic Spine Morphology and Synapse Formation
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DOI：
10.1371/journal.pone.0034677
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发表时间：
2012-04-02
期刊：
影响因子：
3.7
通讯作者：
Song, Woo Keun
中科院分区：
文献类型：
--
作者：
Bae, Jeomil;Sung, Bong Hwan;Song, Woo Keun
背景：树突棘是神经元树突上的膜性突起，接受轴突终末的突触传入。尽管它们对于整合大脑中巨大的信息流非常重要，但调节脊柱形态发生的分子机制还没有得到很好的理解。NESH/Abi-3是Abl相互作用子（Abi）蛋白家族的成员，并且已知其过表达降低细胞运动性和肿瘤转移。NESH是显着表达在大脑中，但其功能仍然unknowed.Methodology/主要发现：NESH强烈表达在海马和适度表达在大脑皮层，小脑和纹状体，在那里它与突触后蛋白PSD 95，SPIN 90和F-肌动蛋白在树突棘共定位。NESH的过表达减少了蘑菇型棘的数量和突触密度，但增加了薄的丝状伪足样棘，对棘密度没有影响。NESH的siRNA敲除也减少了蘑菇棘的数量并抑制了突触的形成，但它增加了棘密度。NESH的N-末端区域共沉淀与丝状肌动蛋白（F-肌动蛋白），这是一个重要的组成部分的树突棘，这表明这种相互作用是重要的树突spines.Conclusions/Significance的成熟：NESH是一种新的F-肌动蛋白结合蛋白，可能起着重要的作用，在调节树突棘的形态发生和突触的形成。
Background: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown.Methodology/Principal Findings: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines.Conclusions/Significance: NESH is a novel F-actin binding protein that likely plays important roles in the regulation of dendritic spine morphogenesis and synapse formation.