PMID- 17475794
OWN - NLM
STAT- MEDLINE
DCOM- 20070606
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 18
DP  - 2007 May 2
TI  - The tyrosine kinase Fyn determines the localization of TrkB receptors in lipid 
      rafts.
PG  - 4859-69
AB  - Localization of Trk neurotrophin receptors is an important factor in directing 
      cellular communication in developing and mature neurons. One potential site of 
      action is in lipid raft membrane microdomains. Although Trk receptors have been 
      localized to lipid rafts, little is known about how these neurotrophin receptors 
      are directed there or how localization to these membrane microdomains regulates 
      Trk signaling. Here, we report that the TrkB brain-derived neurotrophic factor 
      (BDNF) receptor specifically localized to intracellular lipid rafts in cortical 
      and hippocampal membranes in response to BDNF and that this process was 
      critically dependent on the tyrosine kinase Fyn. BDNF-induced TrkB accumulation 
      at lipid rafts was prevented by blocking the internalization of TrkB. BDNF 
      stimulation also resulted in the association between endogenous TrkB and Fyn. 
      Moreover, in neurons derived from Fyn knock-out mice, the translocation of TrkB 
      to lipid rafts in response to BDNF was compromised, whereas the 
      corticohippocampal region of Fyn mutants displayed lower amounts of TrkB in lipid 
      rafts in vivo. In support of a role for lipid rafts in neurotrophin signaling, 
      inhibiting TrkB translocation to lipid rafts, either by using Fyn knock-out 
      neurons or lipid raft-disturbing agents, prevented the full activation of TrkB 
      and of downstream phospholipase C-gamma. These results indicate that the lipid 
      raft localization of TrkB receptors is regulated by Fyn and represents an 
      important factor in determining the outcome of BDNF signaling in neurons.
FAU - Pereira, Daniela B
AU  - Pereira DB
AD  - Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine and 
      Department of Cell Biology, New York University School of Medicine, New York, New 
      York 10016, USA. dp2326@columbia.edu
FAU - Chao, Moses V
AU  - Chao MV
LA  - eng
GR  - NS21072/NS/NINDS NIH HHS/United States
GR  - P01 HD023315/HD/NICHD NIH HHS/United States
GR  - R01 NS021072/NS/NINDS NIH HHS/United States
GR  - R56 NS021072/NS/NINDS NIH HHS/United States
GR  - HD23315/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - Cells, Cultured
MH  - Membrane Microdomains/chemistry/drug effects/*enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-fyn/genetics/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/analysis/genetics/*metabolism
PMC - PMC6672086
EDAT- 2007/05/04 09:00
MHDA- 2007/06/07 09:00
PMCR- 2007/11/02
CRDT- 2007/05/04 09:00
PHST- 2007/05/04 09:00 [pubmed]
PHST- 2007/06/07 09:00 [medline]
PHST- 2007/05/04 09:00 [entrez]
PHST- 2007/11/02 00:00 [pmc-release]
AID - 27/18/4859 [pii]
AID - 3214060 [pii]
AID - 10.1523/JNEUROSCI.4587-06.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 May 2;27(18):4859-69. doi: 10.1523/JNEUROSCI.4587-06.2007.