Wechsler A, Teichberg V I
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
EMBO J. 1998 Jul 15;17(14):3931-9. doi: 10.1093/emboj/17.14.3931.
The N-methyl-D-aspartate receptor (NMDA-R) and brain spectrin, a protein that links membrane proteins to the actin cytoskeleton, are major components of post-synaptic densities (PSDs). Since the activity of the NMDA-R channel is dependent on the integrity of actin and leads to calpain-mediated spectrin breakdown, we have investigated whether the actin-binding spectrin may interact directly with NMDA-Rs. Spectrin is reported here to interact selectively in vitro with the C-terminal cytoplasmic domains of the NR1a, NR2A and NR2B subunits of the NMDA-R but not with that of the AMPA receptor GluR1. Spectrin binds at NR2B sites distinct from those of alpha-actinin-2 and members of the PSD95/SAP90 family. The spectrin-NR2B interactions are antagonized by Ca2+ and fyn-mediated NR2B phosphorylation, but not by Ca2+/calmodulin (CaM) or by Ca2+/CaM-dependent protein kinase II-mediated NR2B phosphorylation. The spectrin-NR1 interactions are unaffected by Ca2+ but inhibited by CaM and by protein kinase A- and C-mediated phosphorylations of NR1. Finally, in rat synaptosomes, both spectrin and NR2B are loosened from membranes upon addition of physiological concentrations of calcium ions. The highly regulated linkage of the NMDA-R to spectrin may underlie the morphological changes that occur in neuronal dendrites concurrently with synaptic activity and plasticity.
N-甲基-D-天冬氨酸受体（NMDA-R）和脑血影蛋白（一种将膜蛋白与肌动蛋白细胞骨架相连的蛋白质）是突触后致密物（PSD）的主要成分。由于NMDA-R通道的活性依赖于肌动蛋白的完整性，并导致钙蛋白酶介导的血影蛋白分解，我们研究了肌动蛋白结合血影蛋白是否可能直接与NMDA-R相互作用。本文报道血影蛋白在体外与NMDA-R的NR1a、NR2A和NR2B亚基的C末端胞质结构域选择性相互作用，但不与AMPA受体GluR1的C末端胞质结构域相互作用。血影蛋白在与α-辅肌动蛋白-2以及PSD95/SAP90家族成员不同的NR2B位点结合。血影蛋白与NR2B的相互作用受到Ca2+和fyn介导的NR2B磷酸化的拮抗，但不受Ca2+/钙调蛋白（CaM）或Ca2+/CaM依赖性蛋白激酶II介导的NR2B磷酸化的影响。血影蛋白与NR1的相互作用不受Ca2+的影响，但受到CaM以及蛋白激酶A和C介导的NR1磷酸化的抑制。最后，在大鼠突触体中，加入生理浓度的钙离子后，血影蛋白和NR2B都从膜上解离。NMDA-R与血影蛋白之间高度调控的联系可能是神经元树突中与突触活动和可塑性同时发生的形态变化的基础。
