PMID- 18353779
OWN - NLM
STAT- MEDLINE
DCOM- 20080617
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 19
DP  - 2008 May 9
TI  - Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated 
      neuronal protection and dendritic growth.
PG  - 13280-8
LID - 10.1074/jbc.M709930200 [doi]
AB  - Endocytosis of Trk (tropomyosin-related kinase) receptors is critical for 
      neurotrophin signal transduction and biological functions. However, the mechanism 
      governing endocytosis of TrkB (tropomyosin-related kinase B) and the specific 
      contributions of TrkB endocytosis to downstream signaling are unknown. In this 
      study, we report that blocking clathrin, dynamin, or AP2 in cultured neurons of 
      the central nervous system inhibited brain-derived neurotrophic factor 
      (BDNF)-induced activation of Akt but not ERK. Treating neurons with the clathrin 
      inhibitor monodansylcadaverine or a peptide that blocks dynamin function 
      specifically abrogated Akt pathway activation in response to BDNF but did not 
      affect the response of other downstream effectors or the up-regulation of 
      immediate early genes neuropeptide Y and activity-regulated 
      cytoskeleton-associated protein. Similar effects were found in neurons expressing 
      small interfering RNA to silence AP2 or a dominant negative form of dynamin that 
      inhibits clathrin-mediated endocytosis. In PC12 cells, ERK but not Akt activation 
      required TrkA endocytosis following stimulation with nerve growth factor, whereas 
      the opposite was true when TrkA-expressing neurons were stimulated with nerve 
      growth factor in the central nervous system. Thus, the specific effects of 
      internalized Trk receptors probably depend on the presence of cell type-specific 
      modulators of neurotrophin signaling and not on differences inherent to Trk 
      receptors themselves. Endocytosis-dependent activation of Akt in neurons was 
      found to be critical for BDNF-supported survival and dendrite outgrowth. 
      Together, these results demonstrate the functional requirement of clathrin- and 
      dynamin-dependent endocytosis in generating the full intracellular response of 
      neurons to BDNF in the central nervous system.
FAU - Zheng, Jing
AU  - Zheng J
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
      Shanghai 200031, China.
FAU - Shen, Wan-Hua
AU  - Shen WH
FAU - Lu, Ting-Jia
AU  - Lu TJ
FAU - Zhou, Yang
AU  - Zhou Y
FAU - Chen, Qian
AU  - Chen Q
FAU - Wang, Zi
AU  - Wang Z
FAU - Xiang, Ting
AU  - Xiang T
FAU - Zhu, Yong-Chuan
AU  - Zhu YC
FAU - Zhang, Chi
AU  - Zhang C
FAU - Duan, Shumin
AU  - Duan S
FAU - Xiong, Zhi-Qi
AU  - Xiong ZQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080319
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Clathrin)
RN  - 0 (Neuropeptide Y)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Clathrin/*metabolism
MH  - Dynamins/metabolism
MH  - Endocytosis/drug effects
MH  - Enzyme Activation/drug effects
MH  - Neurons/*cytology/drug effects/*metabolism
MH  - Neuropeptide Y/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - Tissue Culture Techniques
MH  - Up-Regulation/drug effects
EDAT- 2008/03/21 09:00
MHDA- 2008/06/18 09:00
CRDT- 2008/03/21 09:00
PHST- 2008/03/21 09:00 [pubmed]
PHST- 2008/06/18 09:00 [medline]
PHST- 2008/03/21 09:00 [entrez]
AID - S0021-9258(20)59783-4 [pii]
AID - 10.1074/jbc.M709930200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 May 9;283(19):13280-8. doi: 10.1074/jbc.M709930200. Epub 2008 
      Mar 19.