eprintid: 1508144
rev_number: 29
eprint_status: archive
userid: 608
dir: disk0/01/50/81/44
datestamp: 2016-11-14 15:34:38
lastmod: 2021-12-13 02:18:55
status_changed: 2016-11-14 15:34:38
type: article
metadata_visibility: show
creators_name: Hannan, S
creators_name: Gerrow, K
creators_name: Triller, A
creators_name: Smart, TG
title: Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
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
note: © 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/)
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.
date: 2016-08-16
date_type: published
publisher: CELL PRESS
official_url: http://doi.org/10.1016/j.celrep.2016.07.021
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1148658
doi: 10.1016/j.celrep.2016.07.021
lyricists_name: Hannan, Saad
lyricists_name: Smart, Trevor
lyricists_id: SBHAN72
lyricists_id: TSMAR12
actors_name: Smart, Trevor
actors_id: TSMAR12
actors_role: owner
full_text_status: public
publication: Cell Reports
volume: 16
number: 7
pagerange: 1962-1973
pages: 12
issn: 2211-1247
citation:        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 <https://doi.org/10.1016/j.celrep.2016.07.021>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1508144/1/smart_1-s2.0-S2211124716309202-main.pdf