title: Neuronal activity alters BDNF-TrkB signaling kinetics and downstream functions.
abstract: Differential kinetics of the same signaling pathway might elicit different cellular outcomes. Here, we show that high-frequency neuronal activity converts BDNF-induced TrkB (also known as NTRK2) signaling from a transient to a sustained mode. A prior depolarization (15 mM KCl, 1 hour) resulted in a long-lasting (>24 hours) activation of the TrkB receptor and its downstream signaling, which otherwise lasts less than an hour. The long-term potentiation (LTP)-inducing theta-burst stimulation but not the long-term depression (LTD)-inducing low-frequency stimulation also induced sustained activation of TrkB. This sustained signaling facilitated dendritic branching and rescued neuronal apoptosis induced by glutamate. The change in TrkB signaling kinetics is mediated by Ca(2+) elevation and CaMKII activation, leading to an increase in TrkB expression on the neuronal surface. Physical exercise also alters the kinetics of TrkB phosphorylation induced by exogenous BDNF. Sustained TrkB signaling might serve as a key mechanism underlying the synergistic effects of neuronal activity and BDNF.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Beijing, China School of Medicine, Tsinghua University, 1 Qinghuayuan Road, Beijing, 100084, China School of Life Sciences, Tsinghua University, 1 Qinghuayuan Road, Beijing, 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: GlaxoSmithKline, R&D China, Building 3, 898 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai, 201203, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Beijing, China School of Life Sciences, Tsinghua University, 1 Qinghuayuan Road, Beijing, 100084, China.
authors.forename: Shudan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Beijing, China National Institute of Biological Sciences, Beijing, 102206, China School of Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Beijing, China School of Medicine, Tsinghua University, 1 Qinghuayuan Road, Beijing, 100084, China bai.lu@biomed.tsinghua.edu.cn.
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB
keywords: Neuronal activity; Neuronal surface receptor; Neurotrophin; Signal transduction; Signaling kinetics