PMID- 14559352
OWN - NLM
STAT- MEDLINE
DCOM- 20040226
LR  - 20190827
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 118
IP  - 1-2
DP  - 2003 Oct 21
TI  - Activation of ERK cascade promotes accumulation of Vesl-1S/Homer-1a 
      immunoreactivity at synapses.
PG  - 33-44
AB  - The Vesl-1S/Homer-1a protein is induced during long-term potentiation (LTP), and 
      contains a motif that binds postsynaptic proteins. We have previously reported 
      that synaptic accumulation of Vesl-1S/Homer-1a immunoreactivity (IR) at synapses 
      on the contour of neuronal somata is promoted by stimulation of cells with 
      phorbol esters, 90 mM KCl or proteasome inhibitors. In the present study, we 
      investigated the intracellular mechanism that results in the synaptic 
      accumulation of this protein at synapses. MEK inhibitors completely blocked the 
      effects of phorbol esters and KCl on the accumulation of Vesl-1S/Homer-1a and 
      partially blocked the effect of proteasome inhibitors. Conversely, brain-derived 
      neurotrophic factor (BDNF) and NT3 promoted the accumulation of Vesl-1S/Homer-1a 
      IR at synapses. The extent of this accumulation is correlated with the level of 
      activation of extracellular signal-regulated kinases, ERK following treatment 
      with BDNF. BDNF also caused an increase in the amount of Vesl-1S/Homer-1a 
      protein, but this occurred after Vesl-1S/Homer-1a had accumulated at the 
      synapses. In addition, inhibition of de novo protein synthesis did not affect the 
      phorbol ester-mediated accumulation of Vesl-1S/Homer-1a IR at synapses. These 
      results indicate that activation of the ERK cascade plays a crucial role in the 
      synaptic accumulation of Vesl-1S/Homer-1a IR, and suggest that this accumulation 
      occurs mainly by re-localization of Vesl-1S/Homer-1a protein, and not through an 
      increase in the level of Vesl-1S/Homer-1a. Activity-dependent release of 
      neurotrophins or depolarization may cause local activation of the ERK cascade to 
      produce the synapse-specific localization of Vesl-1S/Homer-1a.
FAU - Kato, Akihiko
AU  - Kato A
AD  - Department of Biology, Faculty of Science, Graduate School of Science, Kyushu 
      University, Higashi, Fukuoka 812-8581, Japan.
FAU - Fukazawa, Yugo
AU  - Fukazawa Y
FAU - Ozawa, Fumiko
AU  - Ozawa F
FAU - Inokuchi, Kaoru
AU  - Inokuchi K
FAU - Sugiyama, Hiroyuki
AU  - Sugiyama H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Homer Scaffolding Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Neuropeptides)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Phorbol Esters)
RN  - 0 (Sodium Channel Blockers)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Action Potentials/physiology
MH  - Animals
MH  - Brain/enzymology
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Cysteine Endopeptidases/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Homer Scaffolding Proteins
MH  - Immunohistochemistry
MH  - MAP Kinase Signaling System/*physiology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Multienzyme Complexes/antagonists & inhibitors/metabolism
MH  - Neurons/drug effects/enzymology
MH  - Neuropeptides/*metabolism
MH  - Neurotrophin 3/pharmacology
MH  - Phorbol Esters/pharmacology
MH  - Potassium Chloride/pharmacology
MH  - Proteasome Endopeptidase Complex
MH  - Rats
MH  - Sodium Channel Blockers/pharmacology
MH  - Synapses/*metabolism
MH  - Synaptic Membranes/drug effects/*enzymology
MH  - Synaptic Transmission/drug effects/physiology
MH  - Up-Regulation/drug effects/physiology
EDAT- 2003/10/16 05:00
MHDA- 2004/02/27 05:00
CRDT- 2003/10/16 05:00
PHST- 2003/10/16 05:00 [pubmed]
PHST- 2004/02/27 05:00 [medline]
PHST- 2003/10/16 05:00 [entrez]
AID - S0169328X0300336X [pii]
AID - 10.1016/j.molbrainres.2003.07.005 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):33-44. doi: 
      10.1016/j.molbrainres.2003.07.005.