title: BDNF-dependent recycling facilitates TrkB translocation to postsynaptic density during LTP via a Rab11-dependent pathway.
abstract: 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.
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Huang
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Sui
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Zhao
authors.initials: Z
authors.lastname: Geng
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019921:Biotinylation; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D057907:Post-Synaptic Density / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020813:Receptor, trkB; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C501449:Dlg4 protein, rat; C109899:Exoc6 protein, rat