BDNF-Dependent Recycling Facilitates TrkB Translocation to Postsynaptic Density during LTP via a Rab11-Dependent Pathway
BDNF-Dependent Recycling Facilitates TrkB Translocation to Postsynaptic Density during LTP via a Rab11-Dependent Pathway
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DOI：
10.1523/jneurosci.3256-12.2013
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发表时间：
2013-05-22
影响因子：
5.3
通讯作者：
Chen, Zhe-Yu
中科院分区：
文献类型：
--
作者：
Huang, Shu-Hong;Wang, Jue;Chen, Zhe-Yu
脑源性神经营养因子（BDNF）通过原肌球蛋白相关激酶B （TrkB）受体激活，在突触结构和功能的活性依赖性调节中发挥重要作用。然而，BDNF是否能够调节长时程增强（LTP）期间突触的TrkB水平尚不清楚。我们在培养的大鼠海马神经元中发现，化学LTP （cLTP）刺激选择性地促进bdnf依赖性全长TrkB （TrkB- fl）受体的内吞循环，而不是通过rab11依赖性途径促进同种异构体T1 （TrkB.T1）受体的内吞循环。此外，神经元活性增强的TrkB-FL循环可以促进受体向突触后密度的易位，增强bdnf诱导的细胞外信号调节激酶和磷脂酰肌醇3-激酶的激活和大鼠海马神经元的存活。最后，我们发现cLTP可以刺激Rab11从无活性形式转变为活性形式，并且gtp结合的Rab11可以增强TrkB-FL与PSD-95之间的相互作用。因此，循环核内体可以作为一个储备池，为LTP维持提供TrkB-FL受体。这些发现提供了rab11依赖的内吞循环和TrkB调节突触可塑性之间的机制联系。
Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function via tropomyosin related kinase B (TrkB) receptor activation. However, whether BDNF could regulate TrkB levels at synapse during long-term potentiation (LTP) is still unknown. We show in cultured rat hippocampal neurons that chemical LTP (cLTP) stimuli selectively promote endocytic recycling of BDNF-dependent full-length TrkB (TrkB-FL) receptors, but not isoform T1 (TrkB.T1) receptors, via a Rab11-dependent pathway. Moreover, neuronal-activity-enhanced TrkB-FL recycling could facilitate receptor translocation to postsynaptic density and enhance BDNF-induced extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation and rat hippocampal neuron survival. Finally, we found that cLTP could stimulate the switch of Rab11 from an inactive to an active form and that GTP-bound Rab11 could enhance the interaction between TrkB-FL and PSD-95. Therefore, the recycling endosome could serve as a reserve pool to supply TrkB-FL receptors for LTP maintenance. These findings provide a mechanistic link between Rab11-dependent endocytic recycling and TrkB modulation of synaptic plasticity.