The C-Terminal Domains of the GABABReceptor Subunits Mediate Intracellular Trafficking But Are Not Required for Receptor Signaling

Intracellular Fluid 0303 health sciences Recombinant Fusion Proteins Amino Acid Motifs Receptors, Cell Surface Transfection Cell Line Protein Structure, Tertiary Rats Protein Subunits Protein Transport 03 medical and health sciences Receptors, GABA-B GTP-Binding Proteins Cricetinae Mutagenesis, Site-Directed Animals Humans Dimerization gamma-Aminobutyric Acid Signal Transduction
DOI: 10.1523/jneurosci.21-04-01203.2001 Publication Date: 2018-04-05T00:12:27Z
ABSTRACT
GABABreceptors are G-protein-coupled receptors that mediate slow synaptic inhibition in the brain and spinal cord. These receptors are heterodimers assembled from GABAB1and GABAB2subunits, neither of which is capable of producing functional GABABreceptors on homomeric expression. GABAB1,although able to bind GABA, is retained within the endoplasmic reticulum (ER) when expressed alone. In contrast, GABAB2is able to access the cell surface when expressed alone but does not couple efficiently to the appropriate effector systems or produce any detectable GABA-binding sites. In the present study, we have constructed chimeric and truncated GABAB1and GABAB2subunits to explore further GABABreceptor signaling and assembly. Removal of the entire C-terminal intracellular domain of GABAB1results in plasma membrane expression without the production of a functional GABABreceptor. However, coexpression of this truncated GABAB1subunit with either GABAB2or a truncated GABAB2subunit in which the C terminal has also been removed is capable of functional signaling via G-proteins. In contrast, transferring the entire C-terminal tail of GABAB1to GABAB2leads to the ER retention of the GABAB2subunit when expressed alone. These results indicate that the C terminal of GABAB1mediates the ER retention of this protein and that neither of the C-terminal tails of GABAB1or GABAB2is an absolute requirement for functional coupling of heteromeric receptors. Furthermore although GABAB1is capable of producing GABA-binding sites, GABAB2is of central importance in the functional coupling of heteromeric GABABreceptors to G-proteins and the subsequent activation of effector systems.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (36)
CITATIONS (135)