PMID- 25903132
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 23
DP  - 2015 Jun 5
TI  - Cyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 
      Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis.
PG  - 14637-46
LID - 10.1074/jbc.M114.627117 [doi]
AB  - The maturation and maintenance of dendritic spines depends on neuronal activity 
      and protein synthesis. One potential mechanism involves mammalian target of 
      rapamycin, which promotes protein synthesis through phosphorylation of 
      eIF4E-binding protein and p70 ribosomal S6 kinase 1 (S6K). Upon extracellular 
      stimulation, mammalian target of rapamycin phosphorylates S6K at Thr-389. S6K 
      also undergoes phosphorylation at other sites, including four serine residues in 
      the autoinhibitory domain. Despite extensive biochemical studies, the importance 
      of phosphorylation in the autoinhibitory domain in S6K function remains 
      unresolved, and its role has not been explored in the cellular context. Here we 
      demonstrated that S6K in neuron was phosphorylated at Ser-411 within the 
      autoinhibitory domain by cyclin-dependent kinase 5. Ser-411 phosphorylation was 
      regulated by neuronal activity and brain-derived neurotrophic factor (BDNF). 
      Knockdown of S6K in hippocampal neurons by RNAi led to loss of dendritic spines, 
      an effect that mimics neuronal activity blockade by tetrodotoxin. Notably, 
      coexpression of wild type S6K, but not the phospho-deficient S411A mutant, could 
      rescue the spine defects. These findings reveal the importance of 
      cyclin-dependent kinase 5-mediated phosphorylation of S6K at Ser-411 in spine 
      morphogenesis driven by BDNF and neuronal activity.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Lai, Kwok-On
AU  - Lai KO
AD  - From the Division of Life Science, Molecular Neuroscience Center and State Key 
      Laboratory of Molecular Neuroscience, The Hong Kong University of Science and 
      Technology, Hong Kong, China laiko@hku.hk.
FAU - Liang, Zhuoyi
AU  - Liang Z
AD  - From the Division of Life Science, Molecular Neuroscience Center and State Key 
      Laboratory of Molecular Neuroscience, The Hong Kong University of Science and 
      Technology, Hong Kong, China.
FAU - Fei, Erkang
AU  - Fei E
AD  - From the Division of Life Science, Molecular Neuroscience Center and State Key 
      Laboratory of Molecular Neuroscience, The Hong Kong University of Science and 
      Technology, Hong Kong, China.
FAU - Huang, Huiqian
AU  - Huang H
AD  - From the Division of Life Science, Molecular Neuroscience Center and State Key 
      Laboratory of Molecular Neuroscience, The Hong Kong University of Science and 
      Technology, Hong Kong, China.
FAU - Ip, Nancy Y
AU  - Ip NY
AD  - From the Division of Life Science, Molecular Neuroscience Center and State Key 
      Laboratory of Molecular Neuroscience, The Hong Kong University of Science and 
      Technology, Hong Kong, China boip@ust.hk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150422
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase 5/*metabolism
MH  - Dendritic Spines/metabolism/*ultrastructure
MH  - Neurons/*cytology/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/analysis/*metabolism
PMC - PMC4505530
OTO - NOTNLM
OT  - BDNF
OT  - brain-derived neurotrophic factor (BDNF)
OT  - cyclin-dependent kinase (CDK)
OT  - dendritic spine
OT  - neuronal activity
OT  - neurotrophin
OT  - phosphorylation
EDAT- 2015/04/24 06:00
MHDA- 2015/08/25 06:00
PMCR- 2016/06/05
CRDT- 2015/04/24 06:00
PHST- 2014/12/14 00:00 [received]
PHST- 2015/04/24 06:00 [entrez]
PHST- 2015/04/24 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
PHST- 2016/06/05 00:00 [pmc-release]
AID - S0021-9258(19)79523-4 [pii]
AID - M114.627117 [pii]
AID - 10.1074/jbc.M114.627117 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Jun 5;290(23):14637-46. doi: 10.1074/jbc.M114.627117. Epub 2015 
      Apr 22.