Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
Neurosci Lett. 2013 Sep 27;552:30-4. doi: 10.1016/j.neulet.2013.07.032. Epub 2013 Jul 31.
Vascular endothelial growth factor (VEGF) and reelin are two major signaling pathways involved in many neuronal functions including neurogenesis and neuronal migration. Both VEGF and reelin have been shown to regulate NMDA type glutamate receptor (NMDAR) activity via independent mechanisms. However, it is not known whether the above signaling pathways influence each other on NMDAR regulation. We demonstrate that Disabled 1 (Dab1), a downstream signaling molecule of reelin pathway mediates VEGF-induced regulation of NMDAR subunit NR2B. Furthermore, VEGF treatment led to the association of VEGF receptor-2 (Flk1) and reelin receptor (apolipoprotein E receptor 2, ApoER2), and Dab1 as well as NR2B activation were Flk1-dependent. Moreover, VEGF treatment could significantly rescue the deficits in phospho-Dab1 levels in reeler (Reln-/-) neurons. Our results suggest a major role of VEGF in the regulation of reelin signaling, and Dab1 as a key molecule in the cross talk between reelin and VEGF signaling pathways.
血管内皮生长因子（VEGF）和 reelin 是参与许多神经元功能的两个主要信号通路，包括神经发生和神经元迁移。已经表明，VEGF 和 reelin 都通过独立的机制来调节 NMDA 型谷氨酸受体（NMDAR）的活性。然而，尚不清楚上述信号通路是否会在 NMDAR 调节方面相互影响。我们证明，reelin 途径的下游信号分子Disabled 1（Dab1）介导了 VEGF 诱导的 NMDAR 亚基 NR2B 的调节。此外，VEGF 处理导致 VEGF 受体-2（Flk1）和 reelin 受体（载脂蛋白 E 受体 2，ApoER2）以及 Dab1 和 NR2B 的激活与 Flk1 有关。此外，VEGF 处理可显著挽救 reeler（Reln-/-）神经元中磷酸化 Dab1 水平的缺陷。我们的研究结果表明，VEGF 在 reelin 信号转导的调节中起着重要作用，Dab1 是 reelin 和 VEGF 信号通路之间串扰的关键分子。
