Hannan, S;
Gerrow, K;
Triller, A;
Smart, TG;
(2016)
Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation.
Cell Reports
, 16
(7)
pp. 1962-1973.
10.1016/j.celrep.2016.07.021.
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Abstract
Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca2+-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783. This signaling cascade indicates how synaptically released glutamate can initiate, via a feedback mechanism, increased levels of presynaptic GABABRs that limit further glutamate release and excitotoxicity.
| Type: | Article |
|---|---|
| Title: | Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2016.07.021 |
| Publisher version: | http://doi.org/10.1016/j.celrep.2016.07.021 |
| Language: | English |
| Additional information: | © 2016 The Author(s). This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, GABA(B) RECEPTOR INTERNALIZATION, GAMMA-AMINOBUTYRIC-ACID, CENTRAL-NERVOUS-SYSTEM, PROTEIN-KINASE, LATERAL MOBILITY, INHIBITORY NEUROTRANSMISSION, HETEROSYNAPTIC DEPRESSION, SURFACE TRAFFICKING, SYNAPTIC PLASTICITY, SUSHI DOMAINS; AMPK; bungarotoxin binding site; Ca2+ signaling; excitotoxicity; GABA receptors; GABAB receptors; glutamate receptors; hippocampus; homeostatic signaling; lateral diffusion; NMDA receptors; phosphorylation; presynaptic terminal; quantum dots; receptor mobility; single-particle tracking; sushi domains |
| 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/1508144 |
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