title: Up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) contributes to BDNF-enhanced neurotransmitter release.
abstract: Brain-derived neurotrophic factor (BDNF) has been implicated in the potent modulation of synaptic plasticity at both pre-synaptic and post-synaptic sites. However, the molecular mechanism underlying BDNF-mediated pre-synaptic modulation remains incompletely understood. Here, we report that BDNF treatment for over 4 h could significantly enhance the expression of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) in cultured hippocampal neurons. This enhancement could be blocked by the Trk inhibitor K252a or by a cAMP response element-binding protein (CREB) inhibitor. In addition, chromatin immunoprecipitation (ChIP) assays revealed that CREB could bind with the JIP3 promoter region and the BDNF treatment could increase this binding. Using dual-luciferase assays we further characterized the cAMP response element (CRE) site in the JIP3 promoter. Finally, we found that BDNF-increased JIP3 expression contributes to the BDNF-induced modulation of neurotransmitter release. Together, our studies reveal that in hippocampal neurons BDNF up-regulates JIP3 expression via CREB activation, which contributes to the enhancement of neurotransmitter release; thus, we have identified a novel mechanism that BDNF modulates pre-synaptic transmission.
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.|Department of Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Bing
authors: B
authors: Chen
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Xin-Liang
authors: XL
authors: Ma
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Zhao
authors: Z
authors: Geng
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Shu-Hong
authors: SH
authors: Huang
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Lu-Kai
authors: LK
authors: Zhai
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Yun-Yun
authors: YY
authors: Guo
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, Jinan, Shandong, China.
authors: Zhe-Yu
authors: ZY
authors: Chen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D050882:CREB-Binding Protein; D048057:Mitogen-Activated Protein Kinase 10
keywords: JIP3; brain-derived neurotrophic factor; cAMP response element-binding protein; hippocampal neurons; neurotransmitter release