title: Myosin Va mediates BDNF-induced postendocytic recycling of full-length TrkB and its translocation into dendritic spines.
abstract: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, neurite outgrowth and synaptic plasticity by activating the receptor tropomyosin receptor kinase B (TrkB, also known as NTRK2). TrkB has been shown to undergo recycling after BDNF stimulation. We have previously reported that full-length TrkB (TrkB-FL) are recycled through a Rab11-dependent pathway upon BDNF stimuli, which is important for the translocation of TrkB-FL into dendritic spines and for the maintenance of prolonged BDNF downstream signaling during long-term potentiation (LTP). However, the identity of the motor protein that mediates the local transfer of recycled TrkB-FL back to the plasma membrane remains unclear. Here, we report that the F-actin-based motor protein myosin Va (Myo5a) mediates the postendocytic recycling of TrkB-FL. Blocking the interaction between Rab11 and Myo5a by use of a TAT-tagged peptide consisting of amino acids 55-66 of the Myo5a ExonE domain weakened the association between TrkB-FL and Myo5a and thus impaired TrkB-FL recycling and BDNF-induced TrkB-FL translocation into dendritic spines. Finally, inhibiting Myo5a-mediated TrkB-FL recycling led to a significant reduction in prolonged BDNF downstream signaling. Taken together, these results show that Myo5a mediates BDNF-dependent TrkB-FL recycling and contributes to BDNF-induced TrkB spine translocation and prolonged downstream signaling.
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China.
authors: Wen-Hai
authors: WH
authors: Sui
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China.
authors: Shu-Hong
authors: SH
authors: Huang
authors: Central Research Laboratory, The Second Hospital of Shandong University, No.247 Beiyuan Dajie, Jinan, Shandong 250033, P.R. China.
authors: Jue
authors: J
authors: Wang
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China.
authors: Qun
authors: Q
authors: Chen
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China.
authors: Ting
authors: T
authors: Liu
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China zheyuchen@sdu.edu.cn.
authors: Zhe-Yu
authors: ZY
authors: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation; D013058:Mass Spectrometry; D051379:Mice; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C513082:Myo5a protein, mouse; D020813:Receptor, trkB; D024701:Myosin Type V; D018995:Myosin Heavy Chains
keywords: BDNF; Myo5a; Myosin Va; NTRK2; Rab11; Recycling; TrkB