TY - JOUR
T1 - BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts
T2 - Roles in synaptic modulation
AU - Suzuki, Shingo
AU - Numakawa, Tadahiro
AU - Shimazu, Kazuhiro
AU - Koshimizu, Hisatsugu
AU - Hara, Tomoko
AU - Hatanaka, Hiroshi
AU - Mei, Lin
AU - Lu, Bai
AU - Kojima, Masami
PY - 2004/12/20
Y1 - 2004/12/20
N2 - Brain-derived neurotrophic factor (BDNF) plays an important role in synoptic 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 synoptic 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 synoptic modulation by BDNF in the central nervous system.
AB - Brain-derived neurotrophic factor (BDNF) plays an important role in synoptic 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 synoptic 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 synoptic modulation by BDNF in the central nervous system.
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U2 - 10.1083/jcb.200404106
DO - 10.1083/jcb.200404106
M3 - Article
C2 - 15596541
AN - SCOPUS:11244275704
SN - 0021-9525
VL - 167
SP - 1205
EP - 1215
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -