Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
J Neurochem. 2010 Jul;114(1):110-21. doi: 10.1111/j.1471-4159.2010.06745.x. Epub 2010 Apr 9.
Tropomyosin-related kinase (Trk) B is a receptor tyrosine kinase for brain-derived neurotrophic factor (BDNF) which plays a critical role in neuronal survival, differentiation and morphogenesis. Ran-binding protein in the microtubule-organizing center (RanBPM) is a cytosolic scaffold protein that has been shown to interact with protein-tyrosine kinase receptor MET, Axl/Sky, and TrkA in addition to the pan-neurotrophin receptor pan-neurotrophin receptor 75 kDa. In this study, we report RanBPM is a novel TrkB-interacting protein that contributes to BDNF-induced MAPK and Akt activation together with neuronal morphogenesis and survival. Over-expression of RanBPM in PC1210 cells (PC12 cells stably over-expressing TrkB) can significantly enhance BDNF-induced MAPK and Akt activation. Moreover, RanBPM can promote BDNF-induced hippocampal neuronal morphogenesis and enhance BDNF-mediated trophic effects after serum deprivation, while siRNA knock down of RanBPM in cells has the opposite effects. Together, these results suggest that RanBPM may modulate TrkB-mediated downstream signaling and biological functions.
原肌球蛋白相关激酶（Trk）B 是脑源性神经营养因子（BDNF）的受体酪氨酸激酶，在神经元存活、分化和形态发生中起着关键作用。微管组织中心的Ran 结合蛋白（RanBPM）是一种胞质支架蛋白，已被证明与蛋白酪氨酸激酶受体 MET、Axl/Sky 和 TrkA 相互作用，此外还与泛神经生长因子受体 75kDa 相互作用。在这项研究中，我们报告 RanBPM 是一种新的 TrkB 相互作用蛋白，它与 BDNF 诱导的 MAPK 和 Akt 激活以及神经元形态发生和存活有关。在 PC1210 细胞（稳定过表达 TrkB 的 PC12 细胞）中过表达 RanBPM 可显著增强 BDNF 诱导的 MAPK 和 Akt 激活。此外，RanBPM 可促进 BDNF 诱导的海马神经元形态发生，并增强血清剥夺后 BDNF 介导的营养作用，而细胞中 RanBPM 的 siRNA 敲低则具有相反的作用。总之，这些结果表明，RanBPM 可能调节 TrkB 介导的下游信号转导和生物学功能。
