Advanced

Glutamine Synthetase Stability and Subcellular Distribution in Astrocytes are Regulated by G-Aminobutyric Type B Receptors.

Huyghe, Deborah; Nakamura, Yasuko; Terunuma, Miho; Faideau, Mathilde LU ; Haydon, Philip; Pangalos, N Mene and Stephen, Moss J (2014) In Journal of Biological Chemistry 289(42). p.28808-28815
Abstract
Emerging evidence suggests that functional γ-aminobutyric acid B receptors (GABABRs) are expressed by astrocytes within the mammalian brain. GABABRs are heterodimeric G-protein coupled receptors that are composed of R1/R2 subunits. To date, they have been characterized in neurons as the principal mediators of sustained inhibitory signaling, however their roles in astrocytic physiology have been ill defined. Here we reveal that the cytoplasmic tail of the GABABR2 subunit binds directly to the astrocytic protein glutamine synthetase (GS) and that this interaction determines the subcellular localization of GS. We further demonstrate that the binding of GS to GABABR2 increases the steady state expression levels of GS in heterologous cells and... (More)
Emerging evidence suggests that functional γ-aminobutyric acid B receptors (GABABRs) are expressed by astrocytes within the mammalian brain. GABABRs are heterodimeric G-protein coupled receptors that are composed of R1/R2 subunits. To date, they have been characterized in neurons as the principal mediators of sustained inhibitory signaling, however their roles in astrocytic physiology have been ill defined. Here we reveal that the cytoplasmic tail of the GABABR2 subunit binds directly to the astrocytic protein glutamine synthetase (GS) and that this interaction determines the subcellular localization of GS. We further demonstrate that the binding of GS to GABABR2 increases the steady state expression levels of GS in heterologous cells and in mouse primary astrocyte culture. Mechanistically this increased stability of GS in the presence of GABABR2 occurs via reduced proteasomal degradation. Collectively, our results suggest a novel role for GABABRs as regulators of GS stability. Given the critical role that GS plays in the glutamine-glutamate cycle, astrocytic GABABRs may play a critical role in supporting both inhibitory and excitatory neurotransmission. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
289
issue
42
pages
28808 - 28815
publisher
ASBMB
external identifiers
  • pmid:25172509
  • wos:000344141000005
  • scopus:84908102200
ISSN
1083-351X
DOI
10.1074/jbc.M114.583534
language
English
LU publication?
yes
id
4c566de3-9d04-4662-bbd1-afb41423f7d3 (old id 4612678)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25172509?dopt=Abstract
date added to LUP
2014-09-09 19:39:38
date last changed
2017-11-12 03:14:30
@article{4c566de3-9d04-4662-bbd1-afb41423f7d3,
  abstract     = {Emerging evidence suggests that functional γ-aminobutyric acid B receptors (GABABRs) are expressed by astrocytes within the mammalian brain. GABABRs are heterodimeric G-protein coupled receptors that are composed of R1/R2 subunits. To date, they have been characterized in neurons as the principal mediators of sustained inhibitory signaling, however their roles in astrocytic physiology have been ill defined. Here we reveal that the cytoplasmic tail of the GABABR2 subunit binds directly to the astrocytic protein glutamine synthetase (GS) and that this interaction determines the subcellular localization of GS. We further demonstrate that the binding of GS to GABABR2 increases the steady state expression levels of GS in heterologous cells and in mouse primary astrocyte culture. Mechanistically this increased stability of GS in the presence of GABABR2 occurs via reduced proteasomal degradation. Collectively, our results suggest a novel role for GABABRs as regulators of GS stability. Given the critical role that GS plays in the glutamine-glutamate cycle, astrocytic GABABRs may play a critical role in supporting both inhibitory and excitatory neurotransmission.},
  author       = {Huyghe, Deborah and Nakamura, Yasuko and Terunuma, Miho and Faideau, Mathilde and Haydon, Philip and Pangalos, N Mene and Stephen, Moss J},
  issn         = {1083-351X},
  language     = {eng},
  number       = {42},
  pages        = {28808--28815},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Glutamine Synthetase Stability and Subcellular Distribution in Astrocytes are Regulated by G-Aminobutyric Type B Receptors.},
  url          = {http://dx.doi.org/10.1074/jbc.M114.583534},
  volume       = {289},
  year         = {2014},
}