BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation.
Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation of TrkB-FL was blocked by Trk inhibitors, suggesting a role of TrkB tyrosine kinase in the translocation. Disruption of lipid rafts by depleting cholesterol from cell surface blocked the ligand-induced translocation. Moreover, disruption of lipid rafts prevented potentiating effects of BDNF on transmitter release in cultured neurons and synaptic response to tetanus in hippocampal slices. In contrast, lipid rafts are not required for BDNF regulation of neuronal survival. Thus, ligand-induced TrkB translocation into lipid rafts may represent a signaling mechanism selective for synaptic modulation by BDNF in the central nervous system.
Suzuki
Shingo
S
Research Institute for Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ikeda, Osaka, Japan.
Numakawa
Tadahiro
T
Shimazu
Kazuhiro
K
Koshimizu
Hisatsugu
H
Hara
Tomoko
T
Hatanaka
Hiroshi
H
Mei
Lin
L
Lu
Bai
B
Kojima
Masami
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB