Wyszynski M, Lin J, Rao A, Nigh E, Beggs A H, Craig A M, Sheng M
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature. 1997 Jan 30;385(6615):439-42. doi: 10.1038/385439a0.
The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechanosensitive and dependent on the integrity of actin, suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton. alpha-Actinin-2, a member of the spectrin/dystrophin family of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95. alpha-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+.
神经递质受体固定于神经元突触后位点的机制在很大程度上尚不清楚。NMDA（N-甲基-D-天冬氨酸）受体的活性具有机械敏感性，且依赖于肌动蛋白的完整性，这表明NMDA受体与突触后细胞骨架之间存在功能上重要的相互作用。α-辅肌动蛋白-2是肌动蛋白结合蛋白的血影蛋白/抗肌萎缩蛋白家族的成员，在此被鉴定为一种脑突触后致密蛋白，它与NMDA受体以及假定的NMDA受体聚集分子PSD-95共定位于树突棘中。α-辅肌动蛋白-2通过其中央杆状结构域与NMDA受体的NR1和NR2B亚基的细胞质尾部结合，并且可以与大鼠脑中的NMDA受体和PSD-95一起进行免疫沉淀。有趣的是，Ca2+/钙调蛋白直接拮抗NR1-α-辅肌动蛋白的结合。因此，α-辅肌动蛋白可能在NMDA受体的定位及其受Ca2+调节中发挥作用。
