PMID- 18474605
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 30
DP  - 2008 Jul 25
TI  - Brain-derived neurotrophic factor-tropomyosin-related kinase B signaling 
      contributes to activity-dependent changes in synaptic proteins.
PG  - 21242-50
LID - 10.1074/jbc.M800282200 [doi]
AB  - The ability of synapses to undergo changes in structure and function in response 
      to alterations of neuronal activity is an essential property of neural circuits. 
      One way that this is achieved is through global changes in the molecular 
      composition of the synapse; however, it is not clear how these changes are 
      coupled to the dynamics of neuronal activity. Here we found that, in cultured rat 
      cortical neurons, bidirectional changes of neuronal activity led to corresponding 
      alterations in the expression of brain-derived neurotrophic factor (BDNF) and 
      phosphorylation of its receptor tropomyosin-related kinase B (TrkB), as well as 
      in the level of synaptic proteins. Exogenous BDNF reversed changes in synaptic 
      proteins induced by chronic activity blockade, while inhibiting Trk kinase 
      activity or depleting endogenous BDNF abolished the concentration changes induced 
      by chronic activity elevation. Both tetrodotoxin and bicuculline had significant, 
      but opposite, effects on synaptic protein ubiquitination in a time-dependent 
      manner. Furthermore, exogenous BDNF was sufficient to increase ubiquitination of 
      synaptic proteins, whereas scavenging endogenous BDNF or inhibiting Trk kinase 
      activity prevented the ubiquitination of synaptic proteins induced by chronic 
      elevation of neuronal activity. Inhibiting the proteasome or blocking protein 
      polyubiquitination mimicked the effect of tetrodotoxin on the levels of synaptic 
      proteins and canceled the effects of BDNF. Our study indicates that BDNF-TrkB 
      signaling acts upstream of the ubiquitin proteasome system, linking neuronal 
      activity to protein turnover at the synapse.
FAU - Jia, Jie-Min
AU  - Jia JM
AD  - Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang 
      Road, Shanghai, China.
FAU - Chen, Qian
AU  - Chen Q
FAU - Zhou, Yang
AU  - Zhou Y
FAU - Miao, Sheng
AU  - Miao S
FAU - Zheng, Jing
AU  - Zheng J
FAU - Zhang, Chi
AU  - Zhang C
FAU - Xiong, Zhi-Qi
AU  - Xiong ZQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080512
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Tropomyosin)
RN  - 0 (Ubiquitin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - DNA/metabolism
MH  - Models, Biological
MH  - Neurons/metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Synapses/*metabolism
MH  - Synaptosomes/metabolism
MH  - Tropomyosin/*metabolism
MH  - Ubiquitin/chemistry
PMC - PMC3258936
EDAT- 2008/05/14 09:00
MHDA- 2008/09/09 09:00
PMCR- 2009/07/25
CRDT- 2008/05/14 09:00
PHST- 2008/05/14 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/05/14 09:00 [entrez]
PHST- 2009/07/25 00:00 [pmc-release]
AID - S0021-9258(19)54747-0 [pii]
AID - 21242 [pii]
AID - 10.1074/jbc.M800282200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Jul 25;283(30):21242-50. doi: 10.1074/jbc.M800282200. Epub 2008 
      May 12.