RanBPM contributes to TrkB signaling and regulates brain-derived neurotrophic factor-induced neuronal morphogenesis and survival.
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.
Yin
Yu-Xia
YX
Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Sun
Zong-Peng
ZP
Huang
Shu-Hong
SH
Zhao
Ling
L
Geng
Zhao
Z
Chen
Zhe-Yu
ZY
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB / Q000502:physiology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases