Ehlers M D, Zhang S, Bernhadt J P, Huganir R L
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cell. 1996 Mar 8;84(5):745-55. doi: 10.1016/s0092-8674(00)81052-1.
NMDA (N-methyl-D-aspartate) receptors are excitatory neurotransmitter receptors in the brain critical for synaptic plasticity and neuronal development. These receptors are Ca2+-permeable glutamate-gated ion channels whose physiological properties are regulated by intracellular Ca2+. We report here the purification of a 20 kDa protein identified as calmodulin that interacts with the NR1 subunit of the NMDA receptor. Calmodulin binding to the NR1 subunit is Ca2+ dependent and occurs with homomeric NR1 complexes, heteromeric NR1/NR2 subunit complexes, and NMDA receptors from brain. Furthermore, calmodulin binding to NR1 causes a 4-fold reduction in NMDA channel open probability. These results demonstrate that NMDA receptor function can be regulated by direct binding of calmodulin to the NR1 subunit, and suggest a possible mechanism for activity-dependent feedback inhibition and Ca2+-dependent inactivation of NMDA receptors.
N-甲基-D-天冬氨酸（NMDA）受体是大脑中的兴奋性神经递质受体，对突触可塑性和神经元发育至关重要。这些受体是Ca2+通透的谷氨酸门控离子通道，其生理特性受细胞内Ca2+调节。我们在此报告一种被鉴定为钙调蛋白的20 kDa蛋白质的纯化，该蛋白与NMDA受体的NR1亚基相互作用。钙调蛋白与NR1亚基的结合依赖于Ca2+，并发生在同聚体NR1复合物、异聚体NR1/NR2亚基复合物以及来自大脑的NMDA受体中。此外，钙调蛋白与NR1的结合导致NMDA通道开放概率降低4倍。这些结果表明，NMDA受体功能可通过钙调蛋白与NR1亚基的直接结合来调节，并提示了NMDA受体活性依赖性反馈抑制和Ca2+依赖性失活的一种可能机制。
