Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by translin-dependent and -independent mechanisms

• Published in: Journal of neurochemistry 2011-03, Vol.116 (6), p.1112-1121
• Main Authors: Wu, Yen-Ching, Williamson, Rebecca, Li, Zhi, Vicario, Annalisa, Xu, Jerry, Kasai, Masataka, Chern, Yijuang, Tongiorgi, Enrico, Baraban, Jay M
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Analysis of Variance; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; CA1 pyramidal neurons; Central nervous system; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Dendrites - drug effects; Dendrites - metabolism; dendritic translation; DNA-Binding Proteins - metabolism; Electrophoretic Mobility Shift Assay - methods; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - cytology; Immunoprecipitation - methods; In Vitro Techniques; Matrix Metalloproteinase 3 - deficiency; Matrix Metalloproteinase 3 - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscarinic Agonists - pharmacology; Neurochemistry; Neurons; Neurons - cytology; Pilocarpine; Pilocarpine - pharmacology; Plasticity (synaptic); Protein transport; Proteins; Pyramidal cells; Ribonucleic acid; RNA; RNA, Messenger - metabolism; RNA, Small Interfering - pharmacology; RNA-binding protein; Signal transduction; Translation; trax; TSN protein; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.07166.x

J. Neurochem. (2011) 116, 1112-1121. 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.