标题：JIP3 Mediates TrkB Axonal Anterograde Transport and Enhances BDNF Signaling by Directly Bridging TrkB with Kinesin-1.
作者：Huang SH;Duan S;Sun T;Wang J;Zhao L;Geng Z;Yan J;Sun HJ;Chen ZY
作者机构：[Huang, S.-H] Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shan 更多
通讯作者地址：[Chen, ZY]Shandong Univ, Sch Med, Dept Neurobiol, Shandong Prov Key Lab Mental Disorders, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
摘要：Brain-derived neurotrophic factor (BDNF), secreted from target tissues, binds and activates TrkB receptors, located on axonal terminals of the innervating neurons, and thereby initiates retrograde signaling. Long-range anterograde transport of TrkB in axons and dendrites requires kinesin-mediated transport. However, it remains unknown whether anterograde TrkB transport mechanisms are the same in axons versus in dendrites. Here, we show that c-Jun NH(2)-terminal kinase-interacting protein 3 (JIP3) binds directly to TrkB, via a minimal 12 aa domain in the TrkB juxtamembrane region, and links TrkB to kinesin-1. The JIP3/TrkB interaction selectively drives TrkB anterograde transport in axons but not in dendrites of rat hippocampal neurons. Moreover, we find that TrkB axonal transport mediated by JIP3 could regulate BDNF-induced Erk activation and axonal filopodia formation. Our findings demonstrate a role for JIP3-mediated TrkB anterograde axonal transport in recruiting more TrkB into distal axons and facilitating BDNF-induced retrograde signaling and synapse modulation, which provides a novel mechanism of how the TrkB anterograde transport can be coupled to BDNF signaling in distal axons.