Glutamine Synthetase Stability and Subcellular Distribution in Astrocytes are Regulated by G-Aminobutyric Type B Receptors.
(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:
https://lup.lub.lu.se/record/4612678
- author
- Huyghe, Deborah ; Nakamura, Yasuko ; Terunuma, Miho ; Faideau, Mathilde LU ; Haydon, Philip ; Pangalos, N Mene and Stephen, Moss J
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 289
- issue
- 42
- pages
- 28808 - 28815
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 10:58:55
- date last changed
- 2022-02-10 07:51:45
@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 = {{American Society for Biochemistry and Molecular Biology}}, 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}}, doi = {{10.1074/jbc.M114.583534}}, volume = {{289}}, year = {{2014}}, }