PMID- 17712061
OWN - NLM
STAT- MEDLINE
DCOM- 20080116
LR  - 20181201
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 22
IP  - 1
DP  - 2008 Jan
TI  - All-trans-retinoic acid stimulates translation and induces spine formation in 
      hippocampal neurons through a membrane-associated RARalpha.
PG  - 236-45
AB  - Differentiation and patterning in the developing nervous system require the 
      vitamin A metabolite all-trans-retinoic acid (atRA). Recent data suggest that 
      higher cognitive functions, such as creation of hippocampal memory, also require 
      atRA and its receptors, RAR, through affecting synaptic plasticity. Here we show 
      that within 30 min atRA increased dendritic growth approximately 2-fold, and 
      PSD-95 and synaptophysin puncta intensity approximately 3-fold, in cultured mouse 
      hippocampal neurons, suggesting increased synapse formation. atRA (10 nM) 
      increased ERK1/2 phosphorylation within 10 min. In synaptoneurosomes, atRA 
      rapidly increased phosphorylation of ERK1/2, its target 4E-BP, and p70S6K, and 
      its substrate, ribosome protein S6, indicating activation of MAPK and mammalian 
      target of rapamycin (mTOR). Immunofluorescence revealed intense dendritic 
      expression of RARalpha in the mouse hippocampus and localization of RARalpha on 
      the surfaces of primary cultures of hippocampal neurons, with bright puncta along 
      soma and neurites. Surface biotinylation confirmed the locus of RARalpha 
      expression. Knockdown of RARalpha by shRNA impaired atRA-induced spine formation 
      and abolished dendritic growth. Prolonged atRA stimulation reduced surface/total 
      RARalpha by 43%, suggesting internalization, whereas brain-derived nerve growth 
      factor or bicuculline increased the ratio by approximately 1.8-fold. atRA 
      increased translation in the somatodendritic compartment, similar to 
      brain-derived nerve growth factor. atRA specifically increased dendritic 
      translation and surface expression of the 
      alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptor (AMPAR) subunit 1 
      (GluR1), without affecting GluR2. These data provide mechanistic insight into 
      atRA function in the hippocampus and identify a unique membrane-associated 
      RARalpha that mediates rapid induction of neuronal translation by atRA.
FAU - Chen, Na
AU  - Chen N
AD  - Nutritional Science and Toxicology, University of California, Berkeley, 
      California 94720, USA.
FAU - Napoli, Joseph L
AU  - Napoli JL
LA  - eng
GR  - AG13566/AG/NIA NIH HHS/United States
GR  - DK36870/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070821
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Rara protein, mouse)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dendrites
MH  - Hippocampus/cytology/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/*drug effects/metabolism
MH  - Protein Biosynthesis/*drug effects
MH  - Receptors, AMPA/metabolism
MH  - Receptors, Retinoic Acid/*drug effects/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Signal Transduction
MH  - Tretinoin/metabolism/*pharmacology
EDAT- 2007/08/23 09:00
MHDA- 2008/01/17 09:00
CRDT- 2007/08/23 09:00
PHST- 2007/08/23 09:00 [pubmed]
PHST- 2008/01/17 09:00 [medline]
PHST- 2007/08/23 09:00 [entrez]
AID - fj.07-8739com [pii]
AID - 10.1096/fj.07-8739com [doi]
PST - ppublish
SO  - FASEB J. 2008 Jan;22(1):236-45. doi: 10.1096/fj.07-8739com. Epub 2007 Aug 21.