BDNF-Dependent Recycling Facilitates TrkB Translocation to Postsynaptic Density during LTP via a Rab11-Dependent Pathway.

Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and func-tion 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 selec-tively promote endocytic recycling of BDNF-dependent full-length TrkB (TrkB-FL) receptors, but not isoform T1 (TrkB.Tl) receptors, via a Rabl 1-dependent pathway. Moreover, neuronal-activity-enhanced TrkB-FL recycling could facilitate receptor translocation to post-synaptic 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 Rabl 1 from an inactive to an active form and that GTP-bound Rabll 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 Rabl 1-dependent endocytic recycling and TrkB modulation of synaptic plasticity. [ABSTRACT FROM AUTHOR]