PMID- 23064382
OWN - NLM
STAT- MEDLINE
DCOM- 20130103
LR  - 20220309
IS  - 1546-1726 (Electronic)
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 15
IP  - 11
DP  - 2012 Nov
TI  - TrkB phosphorylation by Cdk5 is required for activity-dependent structural 
      plasticity and spatial memory.
PG  - 1506-15
LID - 10.1038/nn.3237 [doi]
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB 
      participate in diverse neuronal functions, including activity-dependent synaptic 
      plasticity that is crucial for learning and memory. On binding to BDNF, TrkB is 
      not only autophosphorylated at tyrosine residues but also undergoes serine 
      phosphorylation at S478 by the serine/threonine kinase cyclin-dependent kinase 5 
      (Cdk5). However, the in vivo function of this serine phosphorylation remains 
      unknown. We generated knock-in mice lacking this serine phosphorylation 
      (Trkb(S478A/S478A) mice) and found that the TrkB phosphorylation-deficient mice 
      displayed impaired spatial memory and compromised hippocampal long-term 
      potentiation (LTP). S478 phosphorylation of TrkB regulates its interaction with 
      the Rac1-specific guanine nucleotide exchange factor TIAM1, leading to activation 
      of Rac1 and phosphorylation of S6 ribosomal protein during activity-dependent 
      dendritic spine remodeling. These findings reveal the importance of Cdk5-mediated 
      S478 phosphorylation of TrkB in activity-dependent structural plasticity, which 
      is crucial for LTP and spatial memory formation.
FAU - Lai, Kwok-On
AU  - Lai KO
AD  - Division of Life Science, The Hong Kong University of Science and Technology, 
      Hong Kong, China.
FAU - Wong, Alan S L
AU  - Wong AS
FAU - Cheung, Man-Chun
AU  - Cheung MC
FAU - Xu, Pei
AU  - Xu P
FAU - Liang, Zhuoyi
AU  - Liang Z
FAU - Lok, Ka-Chun
AU  - Lok KC
FAU - Xie, Hui
AU  - Xie H
FAU - Palko, Mary E
AU  - Palko ME
FAU - Yung, Wing-Ho
AU  - Yung WH
FAU - Tessarollo, Lino
AU  - Tessarollo L
FAU - Cheung, Zelda H
AU  - Cheung ZH
FAU - Ip, Nancy Y
AU  - Ip NY
LA  - eng
GR  - Z01 BC010390/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121014
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Quinoxalines)
RN  - 0 (Synaptophysin)
RN  - 0 (T-Lymphoma Invasion and Metastasis-inducing Protein 1)
RN  - 0 (Tiam1 protein, mouse)
RN  - 0 (neuronal Cdk5 activator (p25-p35))
RN  - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
CIN - Nat Neurosci. 2012 Nov;15(11):1474. PMID: 23103993
MH  - Analysis of Variance
MH  - Animals
MH  - Brain/cytology
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase 5/deficiency/*metabolism
MH  - Dendritic Spines/drug effects/metabolism
MH  - Disks Large Homolog 4 Protein
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/genetics
MH  - Glutamic Acid/pharmacology
MH  - Green Fluorescent Proteins/genetics
MH  - Guanine Nucleotide Exchange Factors/metabolism
MH  - Guanylate Kinases/metabolism
MH  - Humans
MH  - Immunoprecipitation/methods
MH  - In Vitro Techniques
MH  - Long-Term Potentiation/drug effects/genetics/*physiology
MH  - Maze Learning/physiology
MH  - Membrane Proteins/metabolism
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mutation/genetics
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurons/drug effects/physiology/ultrastructure
MH  - Phosphorylation/genetics
MH  - Quinoxalines/pharmacology
MH  - Rats
MH  - Receptor, trkB/genetics/*metabolism
MH  - Ribosomal Protein S6 Kinases
MH  - Serine/metabolism
MH  - Silver Staining
MH  - Spatial Behavior/*physiology
MH  - Synaptophysin/metabolism
MH  - T-Lymphoma Invasion and Metastasis-inducing Protein 1
MH  - Time Factors
MH  - Transfection
MH  - rac1 GTP-Binding Protein/metabolism
PMC - PMC7511999
MID - NIHMS1626036
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2012/10/16 06:00
MHDA- 2013/01/04 06:00
PMCR- 2020/09/24
CRDT- 2012/10/16 06:00
PHST- 2012/07/05 00:00 [received]
PHST- 2012/09/13 00:00 [accepted]
PHST- 2012/10/16 06:00 [entrez]
PHST- 2012/10/16 06:00 [pubmed]
PHST- 2013/01/04 06:00 [medline]
PHST- 2020/09/24 00:00 [pmc-release]
AID - nn.3237 [pii]
AID - 10.1038/nn.3237 [doi]
PST - ppublish
SO  - Nat Neurosci. 2012 Nov;15(11):1506-15. doi: 10.1038/nn.3237. Epub 2012 Oct 14.