RanBPM contributes to TrkB signaling and regulates brain-derived neurotrophic factor-induced neuronal morphogenesis and survival

• Published in: Journal of neurochemistry 2010-07, Vol.114 (1), p.110-121
• Main Authors: Yin, Yu-Xia, Sun, Zong-Peng, Huang, Shu-Hong, Zhao, Ling, Geng, Zhao, Chen, Zhe-Yu
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Ageing, cell death; Akt; Animals; Biochemistry and metabolism; Biological and medical sciences; Biology; Brain; Brain-Derived Neurotrophic Factor - physiology; Cell Differentiation; Cell physiology; Cell Survival; Cells, Cultured; Central nervous system; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - physiology; Dendrites - physiology; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Gene expression; Hippocampus - cytology; Humans; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; mortality; neuronal morphogenesis; Neurons; Neurons - physiology; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Phosphatidylinositol 3-Kinases - physiology; Protein Interaction Mapping; Proto-Oncogene Proteins c-akt - metabolism; RanBPM; Rats; Receptor, trkB - physiology; Signal Transduction; survival; TrkB; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06745.x

J. Neurochem. (2010) 114, 110-121. 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.