Hayashi K, Ishikawa R, Ye L H, He X L, Takata K, Kohama K, Shirao T
Department of Neurobiology and Behavior, Gunma University School of Medicine, Japan.
J Neurosci. 1996 Nov 15;16(22):7161-70. doi: 10.1523/JNEUROSCI.16-22-07161.1996.
Morphological changes in the dendritic spines have been postulated to participate in the expression of synaptic plasticity. The cytoskeleton is likely to play a key role in regulating spine structure. Here we examine the molecular mechanisms responsible for the changes in spine morphology, focusing on drebrin, an actin-binding protein that is known to change the properties of actin filaments. We found that adult-type drebrin is localized in the dendritic spines of rat forebrain neurons, where it binds to the cytoskeleton. To identify the cytoskeletal proteins that associated with drebrin, we isolated drebrin-containing cytoskeletons using immunoprecipitation with a drebrin antibody. Drebrin, actin, myosin, and gelsolin were co-precipitated. We next examined the effect of drebrin on actomyosin interaction. In vitro, drebrin reduced the sliding velocity of actin filaments on immobilized myosin and inhibited the actin-activated ATPase activity of myosin. These results suggest that drebrin may modulate the actomyosin interaction within spines and may play a role in the structure-based plasticity of synapses.
树突棘的形态变化被认为参与了突触可塑性的表达。细胞骨架可能在调节棘结构中起关键作用。在这里,我们研究负责棘形态变化的分子机制,重点关注drebrin,一种已知能改变肌动蛋白丝特性的肌动蛋白结合蛋白。我们发现成年型drebrin定位于大鼠前脑神经元的树突棘中,并与细胞骨架结合。为了鉴定与drebrin相关的细胞骨架蛋白,我们使用drebrin抗体通过免疫沉淀分离了含drebrin的细胞骨架。drebrin、肌动蛋白、肌球蛋白和凝溶胶蛋白共沉淀。接下来,我们研究了drebrin对肌动球蛋白相互作用的影响。在体外,drebrin降低了肌动蛋白丝在固定化肌球蛋白上的滑动速度,并抑制了肌球蛋白的肌动蛋白激活的ATP酶活性。这些结果表明,drebrin可能调节棘内的肌动球蛋白相互作用,并可能在基于结构的突触可塑性中发挥作用。