title: Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation.
abstract: BACKGROUND
  Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells.
  
  
  RESULTS
  Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR) is fused with bacterial gyrase B domain (GyrB-PKR), which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis.
  
  
  CONCLUSIONS
  Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.
authors.affiliation: Genes, Cognition and Psychosis Program (GCAP), National Institute of Mental Health/NIH, Bethesda, MD 20892, U.S.A.
authors.forename: H Shawn
authors.initials: HS
authors.lastname: Je
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
mesh_terms: D049933:Aminocoumarins / Q000378:metabolism; D000818:Animals; D027081:DNA Gyrase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D017774:Long-Term Potentiation / Q000502:physiology; D009469:Neuromuscular Junction / Q000033:anatomy & histology / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D046509:Tissue Culture Techniques; D059005:Topoisomerase II Inhibitors; D014982:Xenopus laevis / Q000196:embryology; D019892:eIF-2 Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D049933:Aminocoumarins; D020933:Neurotrophin 3; D011993:Recombinant Fusion Proteins; D059005:Topoisomerase II Inhibitors; D019892:eIF-2 Kinase; D027081:DNA Gyrase; C004628:coumermycin