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.
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20 December 2004
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December 13 2004
BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts : roles in synaptic modulation
Shingo Suzuki,
Shingo Suzuki
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
2Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan
3Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan
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Tadahiro Numakawa,
Tadahiro Numakawa
4National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan
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Kazuhiro Shimazu,
Kazuhiro Shimazu
6Section on Neural Development and Plasticity, NICHD, National Institutes of Health, Bethesda, MD 20892
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Hisatsugu Koshimizu,
Hisatsugu Koshimizu
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
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Tomoko Hara,
Tomoko Hara
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
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Hiroshi Hatanaka,
Hiroshi Hatanaka
2Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan
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Lin Mei,
Lin Mei
5Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912
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Bai Lu,
Bai Lu
6Section on Neural Development and Plasticity, NICHD, National Institutes of Health, Bethesda, MD 20892
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Masami Kojima
Masami Kojima
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
3Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan
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Shingo Suzuki
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
2Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan
3Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan
Tadahiro Numakawa
4National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan
Kazuhiro Shimazu
6Section on Neural Development and Plasticity, NICHD, National Institutes of Health, Bethesda, MD 20892
Hisatsugu Koshimizu
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
Tomoko Hara
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
Hiroshi Hatanaka
2Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan
Lin Mei
5Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912
Bai Lu
6Section on Neural Development and Plasticity, NICHD, National Institutes of Health, Bethesda, MD 20892
Masami Kojima
1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, 563-8577, Japan
3Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan
Correspondence to Masami Kojima: [email protected]; or Bai Lu: [email protected]
Abbreviations used in this paper: 4-AP, 4-amino pyridine; BDNF, brain-derived neurotrophic factor; CNS, central nervous system; GDNF, glial cell line–derived neurotrophic factor; GPI, glycosylphosphatidylinositol; HFS, high frequency stimulation; KRH, Krebs'-Ringer's-Henseleit; LTP, long-term potentiation; MCD, methyl-β-cyclodextrin; PI3-K, phosphatidylinositol 3-kinase; RTK, receptor tyrosine kinase; TrkB-FL, full-length TrkB.
Received:
April 26 2004
Accepted:
October 19 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Government
2004
J Cell Biol (2004) 167 (6): 1205–1215.
Article history
Received:
April 26 2004
Accepted:
October 19 2004
Citation
Shingo Suzuki, Tadahiro Numakawa, Kazuhiro Shimazu, Hisatsugu Koshimizu, Tomoko Hara, Hiroshi Hatanaka, Lin Mei, Bai Lu, Masami Kojima; BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts : roles in synaptic modulation . J Cell Biol 20 December 2004; 167 (6): 1205–1215. doi: https://doi.org/10.1083/jcb.200404106
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