Importance of the γ-Aminobutyric Acid_B Receptor C-Termini for G-Protein Coupling

Molecular Structure and Physiological Functions of GABABReceptors

“…Both groups expressed receptor constructs together with chimeric G qi ␣ or G qo ␣ proteins in HEK293 cells and measured the increase of the intracellular [Ca 2ϩ ] following PLC activation. These findings were confirmed by others who found that the COOH termini of GABA B(1) and GABA B(2) influence G protein coupling but that they are not an absolute requirement for function (125). In contrast, it was reported that the deletion of the GABA B(2) COOH terminus impairs the ability of recombinant receptors to activate Kir3-type K ϩ channels in Xenopus oocytes (211).…”

“…GABA B(1e) is secreted into the culture medium when expressed in transfected mammalian cells. Additionally, it also forms stable heteromeric complexes with GABA B (2) at the plasma membrane, providing additional evidence that the coiled-coil interaction is not the only dimerization interface between GABA B(1) and GABA B(2) (57,125,250). Should the GABA B(1e) protein occur in vivo, then it could affect GABA B receptor function in a dominant-negative manner.…”

“…also observed in other multisubunit proteins, such as, for example, the K ATP channels (355) or N-methyl-D-aspartate (NMDA) receptors (302). It was recently proposed that the sequence context of the RSRR motif in GABA B(1) is crucial for ER retention, and the motif was extended to include the sequence QLQXRQQLRSRR (125). The ERretention signal in GABA B(1) is masked from its ER-anchoring mechanism through the interaction with the COOH terminus of GABA B (2) , thus allowing for delivery of the GABA B (1,2) complex to the cell surface.…”

“…Photoaffinity labeling of GABA B receptors from different species. Brain membranes from the species indicated were labeled with 125 I-CGP71872. In the case of Drosophila melanogaster and Haemonchus concortus, whole animals were analyzed.…”

Glutamate Receptor Trafficking: Endoplasmic Reticulum Quality Control Involves Ligand Binding and Receptor Function

“…Oligomeric proteins assembled in the proper conformation escape ER retention by association and masking of their ER retention/retrieval motifs, whereas improper conformations leave these motifs exposed to COPImediated retrieval. Such mechanisms ensuring that only proper oligomeric forms are expressed on the cell surface were shown recently to regulate trafficking of GluR6 KA receptors (S. , NMDA receptors (Okabe et al, 1999;Standley et al, 2000;Scott et al, 2001), nicotinic acetylcholine receptors (Keller et al, 2001), serotonin type-3 receptors (Boyd et al, 2002), K ϩ channels (Zerangue et al, 1999(Zerangue et al, , 2001Hough et al, 2000), Ca 2ϩ channels , and various G-protein-coupled receptors (Margeta-Mitrovic et al, 2000;Calver et al, 2001;Chan et al, 2001;Pagano et al, 2001;Grunewald et al, 2002).…”