脑源性神经营养因子（BDNF）在调控神经元突起生长及突触可塑性中发挥着关键作用，它的生物学功能主要由神经元膜表面的TrkB受体介导。研究显示,神经元内TrkB正确转运至轴突末端，对于突触前BDNF信号的实现十分重要。我们前期工作发现，在体外培养的海马神经元中JNK相互作用蛋白1（JIP1）与JIP3都参与TrkB的顺轴突转运，并且它们可以协同解除kinesin-1的自抑制。在此基础上，我们将综合运用基因敲除小鼠、坐骨神经结扎、微管结合实验和分子克隆技术，在小鼠体内进一步明确JIP1与JIP3是否协同介导TrkB的顺轴突转运，并研究JIP1与JIP3协同解除kinesin-1自抑制的分子机制，最终将证实这一双分子调控模型是否适用于TrkB之外其他货物的顺轴突转运。本研究有助于深入认识TrkB顺轴突转运的精确调控机制，并为人们更好地理解kinesin-1介导的货物转运调控提供一个参考模型。

Brain-derived neurotrophic factor (BDNF) plays a key role in regulation of neurites outgrowth and synaptic plasticity，which function is mainly mediated by the TrkB receptors. Studies have shown that BDNF signaling in neurons depends on its proper transportation and localization at axon tips. Our previous study has proved that JNK-interacting protein 1 (JIP1) and JIP3 could mediate TrkB axonal anterograde transport and cooperate to release the molecular motor kinesin-1 from autoinhibition. In this project, we will continue to investigate that JIP1 and JIP3 cooperate to mediate TrkB axonal anterograde transport in vivo, by using of transgenic mice and sciatic nerve ligation technology. Then the molecular mechanisms for JIP1 and JIP3 cooperating to release kinesin-1 from autoinhibition will be studied by microtubule binding assay and molecular cloning. At last, we will determine whether JIP1 and JIP3 synergetically actived kinesin-1 is suit for anterograde transport of other cargos besides TrkB. This study aims to in-depth study of the precise regulating mechanisms of TrkB axonal anterograde transport, to provide a model for us to understand the regulation of kinesin-1 mediated cargo trafficking.