Huyghe, D;
Denninger, AR;
Voss, CM;
Frank, P;
Gao, N;
Brandon, N;
Waagepetersen, HS;
... Moss, SJ; + view all
(2019)
Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy.
Frontiers in Molecular Neuroscience
, 12
, Article 120. 10.3389/fnmol.2019.00120.
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Abstract
The astrocyte-specific enzyme glutamine synthetase (GS), which catalyzes the amidation of glutamate to glutamine, plays an essential role in supporting neurotransmission and in limiting NH4+ toxicity. Accordingly, deficits in GS activity contribute to epilepsy and neurodegeneration. Despite its central role in brain physiology, the mechanisms that regulate GS activity are poorly defined. Here, we demonstrate that GS is directly phosphorylated on threonine residue 301 (T301) within the enzyme’s active site by cAMP-dependent protein kinase (PKA). Phosphorylation of T301 leads to a dramatic decrease in glutamine synthesis. Enhanced T301 phosphorylation was evident in a mouse model of epilepsy, which may contribute to the decreased GS activity seen during this trauma. Thus, our results highlight a novel molecular mechanism that determines GS activity under both normal and pathological conditions.
| Type: | Article |
|---|---|
| Title: | Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnmol.2019.00120 |
| Publisher version: | https://doi.org/10.3389/fnmol.2019.00120 |
| Language: | English |
| Additional information: | Copyright © 2019 Huyghe, Denninger, Voss, Frank, Gao, Brandon, Waagepetersen, Ferguson, Pangalos, Doig and Moss. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | glutamine synthetase, phosphorylation, epilepsy, astrocyte, cAMP-dependent protein kinase |
| 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10082346 |
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