Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurones
Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurones
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DOI：
10.1111/j.1471-4159.2005.03536.x
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发表时间：
2006-04-01
影响因子：
4.7
通讯作者：
Shirao, T
中科院分区：
文献类型：
--
作者：
Takahashi, H;Mizui, T;Shirao, T
Dreglycoprotein是脑中主要的F-肌动蛋白结合蛋白。我们最近已经证明，dreplastin A（神经元特异性亚型）簇在突触，并在发育过程中管理突触后密度95蛋白的突触靶向。为了确定dreplastin A对兴奋性突触形成的作用，我们分析了dreplastin A表达的抑制是否影响培养的海马神经元中的丝状伪足-棘形态和NMDA受体的突触靶向。抑制发育程序性上调的dreplastin A的反义治疗显着降低的密度和宽度的丝状伪足棘。免疫细胞化学显示，反义处理并没有减弱突触聚集的NMDA受体的条件下，允许自发活动，但抑制加速的NMDA受体进入突触的拮抗剂d-（-）-2-氨基-5-膦酰基戊酸的靶向。这些结果表明，dreplastin A上调在脊髓形态发生和NMDA受体的活性依赖性突触靶向中起着关键作用。
Drebrin is a major F-actin-binding protein in the brain. We have recently demonstrated that drebrin A (neurone-specific isoform) clusters at synapses and governs targeting of the post-synaptic density 95 protein to synapses during development. To determine the role of drebrin A on excitatory synapse formation, we analysed whether the suppression of drebrin A expression affects filopodia-spine morphology and synaptic targeting of NMDA receptors in cultured hippocampal neurones. Suppression of developmentally programmed up-regulation of drebrin A by antisense treatment significantly decreased the density and width of filopodia-spines. Immunocytochemistry showed that the antisense treatment did not attenuate synaptic clustering of NMDA receptors under conditions that permitted spontaneous activities but inhibited the accelerated targeting of NMDA receptors into synapses by its antagonist d-(-)-2-amino-5-phosphonopentanoic acid. These results indicate that drebrin A up-regulation plays a pivotal role in spine morphogenesis and activity-dependent synaptic targeting of NMDA receptors.