Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
J Neurosci. 2013 May 22;33(21):9214-30. doi: 10.1523/JNEUROSCI.3256-12.2013.
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.
脑源性神经营养因子（BDNF）通过原肌球蛋白相关激酶 B（TrkB）受体的激活，在突触结构和功能的活动依赖性调节中发挥重要作用。然而，BDNF 是否可以在长时程增强（LTP）期间调节突触处的 TrkB 水平尚不清楚。我们在培养的大鼠海马神经元中表明，化学 LTP（cLTP）刺激通过 Rab11 依赖性途径选择性地促进 BDNF 依赖性全长 TrkB（TrkB-FL）受体的内吞循环，而不是同工型 T1（TrkB.T1）受体。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，并增强 BDNF 诱导的细胞外信号调节激酶和磷脂酰肌醇 3-激酶的激活以及大鼠海马神经元的存活。最后，我们发现 cLTP 可以刺激 Rab11 从非活性形式转变为活性形式，并且 GTP 结合的 Rab11 可以增强 TrkB-FL 和 PSD-95 之间的相互作用。因此，内体循环可以作为储备池，为 LTP 维持提供 TrkB-FL 受体。这些发现为 Rab11 依赖性内吞循环和 TrkB 调节突触可塑性之间提供了一种机制联系。
