title: Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by translin-dependent and -independent mechanisms.
abstract: Dendritic trafficking and translation of brain-derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA-mediated knockdown of translin, an RNA-binding protein, impairs KCl-induced dendritic trafficking of BDNF mRNA in cultured hippocampal neurons. We have now assessed whether translin deletion impairs dendritic trafficking of BDNF mRNA in hippocampal neurons in vivo. We have found that translin and its partner protein, trax, undergo dendritic translocation in response to treatment with pilocarpine, a pro-convulsant muscarinic agonist that increases dendritic trafficking of BDNF mRNA in hippocampal neurons. In translin knockout mice, the basal level of dendritic BDNF mRNA is decreased in CA1 pyramidal neurons. However, translin deletion does not block pilocarpine's ability to increase dendritic trafficking of BDNF mRNA indicating that the requirement for translin in this process varies with the stimulus employed to drive it. Consistent with this inference, we found that dendritic trafficking of BDNF mRNA induced by bath application of recombinant BDNF in cultured hippocampal neurons, is not blocked by siRNA-mediated knockdown of translin. Taken together, these in vivo and in vitro findings indicate that dendritic trafficking of BDNF mRNA can be mediated by both translin-dependent and -independent mechanisms.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Wu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Williamson
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Annalisa
authors.initials: A
authors.lastname: Vicario
authors.forename: Jerry
authors.initials: J
authors.lastname: Xu
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasai
authors.forename: Yijuang
authors.initials: Y
authors.lastname: Chern
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: Jay M
authors.initials: JM
authors.lastname: Baraban
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D019278:Matrix Metalloproteinase 3 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498306:Tsnax protein, mouse; D010862:Pilocarpine; D019278:Matrix Metalloproteinase 3