标题：Up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) contributes to BDNF-enhanced neurotransmitter release
作者：Chen, Bing; Ma, Xin-Liang; Geng, Zhao; Huang, Shu-Hong; Zhai, Lu-Kai; Guo, Yun-Yun; Chen, Zhe-Yu
作者机构：[Chen, Bing; Ma, Xin-Liang; Geng, Zhao; Huang, Shu-Hong; Zhai, Lu-Kai; Guo, Yun-Yun; Chen, Zhe-Yu] Shandong Univ, Dept Neurobiol, Shandong Prov Key La 更多
通讯作者地址：[Chen, ZY]Shandong Univ, Sch Med, Dept Neurobiol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：JOURNAL OF NEUROCHEMISTRY
关键词：brain-derived neurotrophic factor; cAMP response element-binding; protein; hippocampal neurons; JIP3; neurotransmitter release
摘要：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 4h 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 theBDNF 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.