Takahashi Hideto, Mizui Toshiyuki, Shirao Tomoaki
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
J Neurochem. 2006 Apr;97 Suppl 1:110-5. doi: 10.1111/j.1471-4159.2005.03536.x.
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.
drebrin是大脑中一种主要的F-肌动蛋白结合蛋白。我们最近证明，drebrin A（神经元特异性亚型）在突触处聚集，并在发育过程中控制突触后致密蛋白95向突触的靶向定位。为了确定drebrin A在兴奋性突触形成中的作用，我们分析了drebrin A表达的抑制是否会影响培养的海马神经元中丝状伪足-棘突的形态以及NMDA受体的突触靶向定位。通过反义处理抑制drebrin A在发育过程中程序性上调，显著降低了丝状伪足-棘突的密度和宽度。免疫细胞化学显示，在允许自发活动的条件下，反义处理并未减弱NMDA受体的突触聚集，但抑制了其拮抗剂D-(-)-2-氨基-5-磷酸戊酸使NMDA受体加速靶向进入突触。这些结果表明，drebrin A的上调在棘突形态发生和NMDA受体的活性依赖性突触靶向中起关键作用。
