神经元活性调控TrkB受体再循环的机制研究

项目名称： 神经元活性调控TrkB受体再循环的机制研究

项目编号： No.31271519

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 黄淑红

作者单位： 山东大学

项目金额： 80万元

中文摘要： 脑源性神经营养因子(BDNF)不仅能促进神经元的存活、分化、树突和轴突的生长，而且在调节突触可塑性中起着关键作用，它的生物学功能主要由TrkB受体介导。研究显示神经元活性可以调节BDNF对神经元的作用，使BDNF能选择性地作用于高活性的神经元。我们前期研究发现神经元活性可以显著减少TrkB内吞后进入降解途径，从而使更多的TrkB进入再循环途径回到细胞膜上。这提示神经元活性对BDNF的调节作用，在一定程度上是通过增加TrkB受体内吞后再循环来增加其在细胞膜表面的分布。但是调控这一过程的分子机制目前尚不清楚！本项目将研究神经元活性调控TrkB受体再循环的分子机制，以及这种活性依赖的TrkB再循环对BDNF生物学功能的影响。本研究旨在研究活性调控TrkB受体再循环的分子机制及其相应的生物学意义，有助于我们深入了解BDNF的作用机制。

中文关键词： 脑源性神经营养因子；TrkB受体；Rab11；再循环；神经元活性

英文摘要： Brain-derived neurotrophic factor (BDNF) not only can promote neuron survival, differentiation, dendrites and axon growth, but also plays a key role in regulating synaptic plasticity. The biological functions of BDNF were mainly mediated by the TrkB receptor. Studies have shown that neuronal activity can regulate the effect of BDNF on neurons. BDNF can selectively act on the of neurons with high activity. Our previous study found that neuronal activity can significantly reduce the internalized TrkB being sorted into the degradation pathway, so more TrkB can enter the recycling pathway back to the cell surface. The results suggest that the regulation of neuronal activity on BDNF, to a certain extent, is through increasing the recycling of TrkB receptor to increase its distribution in the cell surface. But the molecular mechanism of regulation of this process is not yet clear. This project will study the molecular mechanisms of neuronal activity dependent TrkB receptor recycling, and the biological functions of activity-dependent TrkB recycling. This study aimed to in-depth study of the molecular mechanism of activity-dependent TrkB recycling and its biological significance, to help our further understanding of the role of BDNF.

英文关键词： BDNF；TrkB receptor；Rab11；recycling；neural activity