PMID- 18499195
OWN - NLM
STAT- MEDLINE
DCOM- 20081105
LR  - 20141120
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 55
IP  - 1
DP  - 2008 Jul
TI  - The role of RIM1alpha in BDNF-enhanced glutamate release.
PG  - 27-34
LID - 10.1016/j.neuropharm.2008.04.009 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is known to activate proline-directed 
      Ser/Thr protein kinases and to enhance glutamatergic transmission via a 
      Rab3a-dependent molecular pathway. The identity of molecular targets in BDNF's 
      action on Rab3a pathway, a synaptic vesicle protein involved in vesicle 
      trafficking and synaptic plasticity, is not fully known. Here we demonstrate that 
      BDNF enhances depolarization-evoked efflux of [(3)H]-glutamate from nerve 
      terminals isolated from the CA1 region of the hippocampus. BDNF also potentiated 
      hyperosmotic shock-evoked [(3)H]-glutamate efflux, indicating an effect on the 
      size of the readily releasable pool. This effect of BDNF was completely abolished 
      in nerve terminals derived from Rim1alphaKO (Rab3 interacting molecule 1alpha 
      null mutant) mice. Using in vitro phosphorylation assays we identified two novel 
      phosphorylation sites, Ser447 and Ser745 that were substrates for ERK2, a 
      proline-directed kinase known to be activated by BDNF. The pSer447 site was 
      phosphorylated under resting conditions in hippocampal CA1 nerve terminals and 
      its phosphorylation was enhanced by BDNF treatment, as indicated by the use of a 
      pSer447-RIM1alpha antibody we have developed. Together these findings identify 
      RIM1alpha, a component of the Rab3a molecular pathway in mediating presynaptic 
      plasticity, as a necessary factor in BDNF's enhancement of [(3)H]-glutamate 
      efflux from hippocampal CA1 nerve terminals and indicate a possible role for 
      RIM1alpha phosphorylation in BDNF-dependent presynaptic plasticity.
FAU - Simsek-Duran, Fatma
AU  - Simsek-Duran F
AD  - Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 W. 
      Olney Road Norfolk, VA 23507, USA.
FAU - Lonart, Gyorgy
AU  - Lonart G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080422
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Rims1 protein, mouse)
RN  - 0 (Sweetening Agents)
RN  - 10028-17-8 (Tritium)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 452VLY9402 (Serine)
RN  - 57-50-1 (Sucrose)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 2)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - GTP-Binding Proteins/deficiency/*physiology
MH  - Gene Expression Regulation, Enzymologic/drug effects/genetics
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/ultrastructure
MH  - In Vitro Techniques
MH  - MAP Kinase Kinase Kinase 2/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phosphorylation/drug effects
MH  - Serine/metabolism
MH  - Sucrose/pharmacology
MH  - Sweetening Agents/pharmacology
MH  - Synaptosomes/*drug effects/*metabolism
MH  - Time Factors
MH  - Tritium/metabolism
EDAT- 2008/05/24 09:00
MHDA- 2008/11/06 09:00
CRDT- 2008/05/24 09:00
PHST- 2007/12/01 00:00 [received]
PHST- 2008/03/14 00:00 [revised]
PHST- 2008/04/11 00:00 [accepted]
PHST- 2008/05/24 09:00 [pubmed]
PHST- 2008/11/06 09:00 [medline]
PHST- 2008/05/24 09:00 [entrez]
AID - S0028-3908(08)00102-0 [pii]
AID - 10.1016/j.neuropharm.2008.04.009 [doi]
PST - ppublish
SO  - Neuropharmacology. 2008 Jul;55(1):27-34. doi: 10.1016/j.neuropharm.2008.04.009. 
      Epub 2008 Apr 22.