PMID- 22736542
OWN - NLM
STAT- MEDLINE
DCOM- 20130627
LR  - 20161125
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 22
IP  - 12
DP  - 2012 Dec
TI  - Protein kinase C stimulates HuD-mediated mRNA stability and protein expression of 
      neurotrophic factors and enhances dendritic maturation of hippocampal neurons in 
      culture.
PG  - 2303-19
LID - 10.1002/hipo.22048 [doi]
AB  - HuD protein is an RNA-binding protein involved in post-transcriptional regulation 
      of gene expression for synaptogenesis, neuronal differentiation, and learning and 
      memory, and is up-regulated and redistributed by a protein kinase C 
      (PKC)-dependent pathway in neurons. Here, we show a PKC-regulated mechanism on 
      HuD-mediated mRNA stability and expression of several neurotrophic factors (NTFs) 
      in cultured hippocampal neurons. HuD pull-down assays showed that HuD is 
      associated with brain-derived neurotrophic factor (BDNF), nerve growth factor 
      (NGF), and neurotrophin (NT)-3 mRNAs. Reduction of HuD expression with short 
      hairpin RNAs decreased BDNF, NGF, and NT-3 mRNAs and NTFs expression. Bryostatin, 
      a PKC activator, treatment enhanced their association with HuD and increased 
      these transcripts' stability. Bryostatin induced HuD phosphorylation, which was 
      inhibited by Ro 32-0432, a specific PKC inhibitor. Activated PKC specifically 
      phosphorylated coactivator-associated arginine methyltransferase 1 (CARM1), which 
      methylates HuD and negatively modulates HuD-mRNA interactions during neuronal 
      differentiation, and inhibited its methyltransferase activity, resulting in 
      decrease in CARM1-mediated HuD methylation. Furthermore cotreatment of bryostatin 
      and AMI-1, a specific CARM1 inhibitor, potentiated PKC-dependent HuD-mRNA 
      interactions and enhanced dendritic arborization. These results demonstrate that 
      PKC may play an important role in neuronal differentiation and synaptogenesis via 
      stimulating HuD-mediated mRNA stability and inhibiting CARM1 in hippocampal 
      neurons.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Lim, Chol Seung
AU  - Lim CS
AD  - Blanchette Rockefeller Neurosciences Institute at West Virginia University, 
      Morgantown, WV 26505, USA. clim@brni.org
FAU - Alkon, Daniel L
AU  - Alkon DL
LA  - eng
PT  - Journal Article
DEP - 20120627
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (ELAV Proteins)
RN  - 0 (ELAV-Like Protein 4)
RN  - 0 (Elavl4 protein, rat)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
RN  - EC 2.1.1.319 (coactivator-associated arginine methyltransferase 1)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Chromatography, High Pressure Liquid
MH  - Dendrites/metabolism/ultrastructure
MH  - ELAV Proteins/*metabolism
MH  - ELAV-Like Protein 4
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Hippocampus/metabolism/ultrastructure
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Mass Spectrometry
MH  - Nerve Growth Factors/*biosynthesis
MH  - Neurogenesis/*physiology
MH  - Neurons/metabolism/ultrastructure
MH  - Protein Kinase C/*metabolism
MH  - Protein-Arginine N-Methyltransferases/*metabolism
MH  - RNA Stability
MH  - RNA, Messenger
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/physiology
EDAT- 2012/06/28 06:00
MHDA- 2013/06/29 06:00
CRDT- 2012/06/28 06:00
PHST- 2012/06/01 00:00 [accepted]
PHST- 2012/06/28 06:00 [entrez]
PHST- 2012/06/28 06:00 [pubmed]
PHST- 2013/06/29 06:00 [medline]
AID - 10.1002/hipo.22048 [doi]
PST - ppublish
SO  - Hippocampus. 2012 Dec;22(12):2303-19. doi: 10.1002/hipo.22048. Epub 2012 Jun 27.