Chen H J, Rojas-Soto M, Oguni A, Kennedy M B
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Neuron. 1998 May;20(5):895-904. doi: 10.1016/s0896-6273(00)80471-7.
Ca2+ influx through N-methyl-D-aspartate- (NMDA-) type glutamate receptors plays a critical role in synaptic plasticity in the brain. One of the proteins activated by the increase in Ca2+ is CaM kinase II (CaMKII). Here, we report a novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major component of the postsynaptic density, a complex of proteins associated with synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses in hippocampal neurons where it binds to and closely colocalizes with the scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors.
通过N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体的Ca2+内流在大脑突触可塑性中起关键作用。因Ca2+增加而被激活的一种蛋白质是钙调蛋白激酶II（CaMKII）。在此，我们报告了一种新型的突触Ras-GTP酶激活蛋白（p135 SynGAP），它是突触后致密区的主要成分，突触后致密区是与突触NMDA受体相关的蛋白质复合物。p135 SynGAP几乎只定位于海马神经元的突触，在那里它与支架蛋白PSD-95结合并紧密共定位，且与NMDA受体共定位。位于PSD蛋白复合物中的CaMKII磷酸化可抑制p135 SynGAP的Ras-GTP酶激活活性。CaMKII对p135 SynGAP的抑制作用将阻止结合GTP的Ras失活，因此在NMDA受体激活后可能导致海马神经元中的丝裂原活化蛋白（MAP）激酶途径激活。
