Takasu Mari A, Dalva Matthew B, Zigmond Richard E, Greenberg Michael E
Division of Neuroscience, Children's Hospital, and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Science. 2002 Jan 18;295(5554):491-5. doi: 10.1126/science.1065983. Epub 2001 Dec 20.
Protein-protein interactions and calcium entry through the N-methyl-d-aspartate (NMDA)-type glutamate receptor regulate synaptic development and plasticity in the central nervous system. The EphB receptor tyrosine kinases are localized at excitatory synapses where they cluster and associate with NMDA receptors. We identified a mechanism whereby EphBs modulate NMDA receptor function. EphrinB2 activation of EphB in primary cortical neurons potentiates NMDA receptor-dependent influx of calcium. Treatment of cells with ephrinB2 led to NMDA receptor tyrosine phosphorylation through activation of the Src family of tyrosine kinases. These ephrinB2-dependent events result in enhanced NMDA receptor-dependent gene expression. Our findings indicate that ephrinB2 stimulation of EphB modulates the functional consequences of NMDA receptor activation and suggest a mechanism whereby activity-independent and activity-dependent signals converge to regulate the development and remodeling of synaptic connections.
蛋白质-蛋白质相互作用以及通过N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体的钙内流调节中枢神经系统中的突触发育和可塑性。EphB受体酪氨酸激酶定位于兴奋性突触，在那里它们聚集并与NMDA受体相关联。我们确定了一种EphB调节NMDA受体功能的机制。原代皮质神经元中ephrinB2对EphB的激活增强了NMDA受体依赖性的钙内流。用ephrinB2处理细胞通过激活酪氨酸激酶Src家族导致NMDA受体酪氨酸磷酸化。这些依赖于ephrinB2的事件导致增强的NMDA受体依赖性基因表达。我们的研究结果表明，ephrinB2对EphB的刺激调节了NMDA受体激活的功能后果，并提出了一种机制，通过该机制，非活性依赖性和活性依赖性信号汇聚以调节突触连接的发育和重塑。
