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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Deborah Huyghe
  • Yasuko Nakamura
  • Miho Terunuma
  • Mathilde Faideau
  • Philip Haydon
  • N Mene Pangalos
  • Moss J Stephen
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)28808-28815
JournalJournal of Biological Chemistry
Volume289
Issue number42
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes