Jovanovic, JN;
Thomas, P;
Kittler, JT;
Smart, TG;
Moss, SJ;
(2004)
Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability.
J NEUROSCI
, 24
(2)
522 - 530.
10.1523/JNEUROSCI.3606-03.2004.
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Abstract
The efficacy of GABAergic synaptic inhibition is a principal factor in controlling neuronal activity. We demonstrate here that brain-derived neurotrophic factor modulates the activity of GABA(A) receptors, the main sites of fast synaptic inhibition in the brain, within minutes of application. Temporally, this comprised an early enhancement in the miniature IPSC amplitude, followed by a prolonged depression. This modulation was concurrent with enhanced PKC-mediated phosphorylation, followed by protein phosphatase 2A (PP2A)-mediated dephosphorylation of the GABA(A) receptor. Mechanistically, these events were facilitated by differential recruitment of PKC, receptor for activated C-kinase, and PP2A to GABA(A) receptors, depending on the phosphorylation state of the receptor beta(3)-subunit. Thus, transient formation of GABA(A) receptor signaling complexes has the potential to provide a basis for acute changes in receptor function underlying GABAergic synaptic plasticity.
| Type: | Article |
|---|---|
| Title: | Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/JNEUROSCI.3606-03.2004 |
| Publisher version: | http://dx.doi.org/10.1523/JNEUROSCI.3606-03.2004 |
| Language: | English |
| Additional information: | This work is available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license. |
| Keywords: | GABA, growth factor, phosphatase, phosphorylation, protein kinase, synaptic, PROTEIN-KINASE-C, A RECEPTOR, INTRACELLULAR DOMAINS, FUNCTIONAL MODULATION, CORTICAL-NEURONS, AMPA RECEPTORS, BETA SUBUNITS, ION CHANNELS, FACTOR BDNF, RAT-BRAIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/122668 |
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