Journal article
The role of RIM1α in BDNF-enhanced glutamate release
Neuropharmacology, Vol.55(1), pp.27-34
2008
DOI: 10.1016/j.neuropharm.2008.04.009
PMID: 18499195
Abstract
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 [
3H]-glutamate from nerve terminals isolated from the CA1 region of the hippocampus. BDNF also potentiated hyperosmotic shock-evoked [
3H]-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
Rim1αKO (Rab3 interacting molecule 1α 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-RIM1α antibody we have developed. Together these findings identify RIM1α, a component of the Rab3a molecular pathway in mediating presynaptic plasticity, as a necessary factor in BDNF's enhancement of [
3H]-glutamate efflux from hippocampal CA1 nerve terminals and indicate a possible role for RIM1α phosphorylation in BDNF-dependent presynaptic plasticity.
Details
- Title: Subtitle
- The role of RIM1α in BDNF-enhanced glutamate release
- Creators
- Fatma Simsek-DuranGyörgy Lonart
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.55(1), pp.27-34
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.neuropharm.2008.04.009
- PMID
- 18499195
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Grant note
- DOI: 10.13039/100006990, name: Thomas F. and Kate Miller Jeffress Memorial Trust; DOI: 10.13039/100013759, name: Commonwealth Health Research Board
- Language
- English
- Date published
- 2008
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003964802771
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