PMID- 14623964
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 100
IP  - 24
DP  - 2003 Nov 25
TI  - BDNF induces translocation of initiation factor 4E to mRNA granules: evidence for 
      a role of synaptic microfilaments and integrins.
PG  - 14403-8
AB  - In many cell types, translation can be regulated by a redistribution of 
      translation initiation factors to actin-based cytoskeletal compartments that 
      contain bound mRNAs. This process is evoked by extracellular signals and is 
      regulated by determinants of cytoskeletal organization, such as integrins. In the 
      present experiments, we provide evidence that similar mechanisms regulate local 
      translation in dendrites during synaptic plasticity. Treatment of various 
      neuronal preparations with the brain-derived neurotrophic factor (BDNF) resulted 
      in redistribution of the critical eukaryotic initiation factor 4E (eIF4E) to an 
      mRNA granule-rich cytoskeletal fraction isolated from detergent-solubilized 
      samples. eIF4E linkage to cap structures mediates the recruitment of other 
      translation factors in the initiation of translation events. Immunoprecipitation 
      studies confirmed that eIF4E associates with mRNA granules and that BDNF 
      increased this association. BDNF-induced redistribution of eIF4E was blocked by 
      preincubation with either a peptide (GRGDSP) that inhibits integrin-matrix 
      interactions or by a high concentration (20 microM) of the F-actin depolymerizing 
      agent latrunculin A. Immunohistochemical studies in cultured neurons demonstrated 
      that BDNF facilitated translocation of eIF4E into dendritic spines. Together, the 
      findings suggest that BDNF regulates translation in dendrites by altering the 
      localization of eIF4E relative to cytoskeletally bound mRNA granules. Integrins, 
      which are known to be essential for stabilizing certain forms of synaptic 
      plasticity, may be critical regulators of local translation events at synapses.
FAU - Smart, Fiona M
AU  - Smart FM
AD  - Department of Neurobiology, The Scripps Research Institute, and The Skaggs 
      Institute for Chemical Biology, La Jolla, CA 92037, USA.
FAU - Edelman, Gerald M
AU  - Edelman GM
FAU - Vanderklish, Peter W
AU  - Vanderklish PW
LA  - eng
GR  - K01 MH064036/MH/NIMH NIH HHS/United States
GR  - R01 HD009635/HD/NICHD NIH HHS/United States
GR  - HD09635/HD/NICHD NIH HHS/United States
GR  - MH64036/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031117
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Integrins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Actin Cytoskeleton/metabolism
MH  - Actins/metabolism
MH  - Animals
MH  - Biological Transport, Active/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Dendrites/drug effects/metabolism
MH  - Eukaryotic Initiation Factor-4E/*metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - In Vitro Techniques
MH  - Integrins/*metabolism
MH  - Protein Biosynthesis/drug effects
MH  - RNA, Messenger/genetics/*metabolism
MH  - Rats
MH  - Recombinant Proteins/pharmacology
MH  - Subcellular Fractions/metabolism
MH  - Synapses/*drug effects/*metabolism
PMC - PMC283604
EDAT- 2003/11/19 05:00
MHDA- 2004/02/03 05:00
PMCR- 2004/05/25
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
PHST- 2004/05/25 00:00 [pmc-release]
AID - 2436349100 [pii]
AID - 10014403 [pii]
AID - 10.1073/pnas.2436349100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14403-8. doi: 
      10.1073/pnas.2436349100. Epub 2003 Nov 17.