These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activation mechanism of the heterodimeric GABA(B) receptor.
    Author: Pin JP, Kniazeff J, Binet V, Liu J, Maurel D, Galvez T, Duthey B, Havlickova M, Blahos J, Prézeau L, Rondard P.
    Journal: Biochem Pharmacol; 2004 Oct 15; 68(8):1565-72. PubMed ID: 15451400.
    Abstract:
    The GABA(B) receptor was the first heteromeric G-protein coupled receptor (GPCR) identified. Indeed, both GABA(B1) and GABA(B2) subunits appear necessary to get a functional GABA(B) receptor. Soon after the cloning of both subunits, it was demonstrated that GABA(B2) was required for GABA(B1) to reach the cell surface. However, even a mutated GABA(B1) able to reach the cell surface is not functional alone despite its ability to bind GABA(B) ligands. This clearly demonstrated that GABA(B2) is not only required for the correct trafficking of GABA(B1) but also for the correct functioning of the receptor. In the present review article, we will summarize our actual knowledge of the specific role of each subunit in ligand recognition, intramolecular transduction, G-protein activation and allosteric modulation. We will show that the GABA(B) receptor is an heterodimer (not an hetero-oligomer), that agonists bind in GABA(B1), whereas GABA(B2) controls agonist affinity and is responsible for G-protein coupling. Finally, we will show that the recently identified positive allosteric modulator CGP7930 acts as a direct activator of the heptahelical domain of GABA(B2), being therefore the first GABA(B2) ligand identified so far.
    [Abstract] [Full Text] [Related] [New Search]