PMID- 24271058
OWN - NLM
STAT- MEDLINE
DCOM- 20150115
LR  - 20211021
IS  - 1573-9546 (Electronic)
IS  - 1573-9538 (Print)
IS  - 1573-9538 (Linking)
VI  - 10
IP  - 2
DP  - 2014
TI  - Regulation of TrkB receptor translocation to lipid rafts by adenosine A(2A) 
      receptors and its functional implications for BDNF-induced regulation of synaptic 
      plasticity.
PG  - 251-67
AB  - Brain-derived neurotrophic factor (BDNF) signalling is critical for neuronal 
      development and transmission. Recruitment of TrkB receptors to lipid rafts has 
      been shown to be necessary for the activation of specific signalling pathways and 
      modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to 
      be modulated by adenosine A(2A) receptor activation, we hypothesized that 
      activation of A(2A) receptors could influence TrkB receptor localization among 
      different membrane microdomains. We found that adenosine A(2A) receptor agonists 
      increased the levels of TrkB receptors in the lipid raft fraction of cortical 
      membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels 
      in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansyl 
      cadaverine (100 muM) did not modify the effects of the A(2A) receptor agonists, 
      but significantly impaired BDNF effects on TrkB recruitment to lipid rafts. The 
      effect of A(2A) receptor activation in TrkB localization was mimicked by 5 muM 
      forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA 
      inhibitors RpcAMPs and PKI-(14-22) and by the Src-family kinase inhibitor PP2. 
      Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced 
      BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid 
      raft integrity was also required for the effects of BDNF upon hippocampal 
      long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, 
      a BDNF-independent recruitment of TrkB receptors to lipid rafts, induced by the 
      activation of adenosine A(2A) receptors, with functional consequences for TrkB 
      phosphorylation and BDNF-induced modulation of neurotransmitter release and 
      hippocampal plasticity.
FAU - Assaife-Lopes, Natalia
AU  - Assaife-Lopes N
FAU - Sousa, Vasco C
AU  - Sousa VC
FAU - Pereira, Daniela B
AU  - Pereira DB
FAU - Ribeiro, Joaquim A
AU  - Ribeiro JA
FAU - Sebastiao, Ana M
AU  - Sebastiao AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131123
PL  - Netherlands
TA  - Purinergic Signal
JT  - Purinergic signalling
JID - 101250499
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptor, Adenosine A2A)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Membrane Microdomains/metabolism
MH  - Neuronal Plasticity/*physiology
MH  - Neurons/*metabolism
MH  - Organ Culture Techniques
MH  - Patch-Clamp Techniques
MH  - Protein Transport/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Receptor, Adenosine A2A/*metabolism
MH  - Receptor, trkB/*metabolism
MH  - Synaptic Transmission/physiology
PMC - PMC4040169
EDAT- 2013/11/26 06:00
MHDA- 2015/01/16 06:00
PMCR- 2014/02/20
CRDT- 2013/11/26 06:00
PHST- 2013/09/14 00:00 [received]
PHST- 2013/09/24 00:00 [accepted]
PHST- 2013/11/26 06:00 [entrez]
PHST- 2013/11/26 06:00 [pubmed]
PHST- 2015/01/16 06:00 [medline]
PHST- 2014/02/20 00:00 [pmc-release]
AID - 9383 [pii]
AID - 10.1007/s11302-013-9383-2 [doi]
PST - ppublish
SO  - Purinergic Signal. 2014;10(2):251-67. doi: 10.1007/s11302-013-9383-2. Epub 2013 
      Nov 23.