First Author | Chen B | Year | 2015 |
Journal | J Neurochem | Volume | 135 |
Issue | 3 | Pages | 453-65 |
PubMed ID | 26303065 | Mgi Jnum | J:227086 |
Mgi Id | MGI:5699654 | Doi | 10.1111/jnc.13226 |
Citation | Chen B, et al. (2015) Up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) contributes to BDNF-enhanced neurotransmitter release. J Neurochem 135(3):453-65 |
abstractText | 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. We demonstrated that in hippocampal neurons BDNF/TrkB signaling mediates transcriptional up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) via CREB activation. The up-regulation of JIP3 further contributes to BDNF-enhanced neurotransmitter release. These findings provide insight into the mechanistic link between BDNF-mediated gene expression and its more sustained pre-synaptic modulation, which may help us to further understand the roles of BDNF in neuronal plasticity. |