INTRACELLULAR RETENTION OF RECOMBINANT GABA(B) RECEPTORS

gamma-Aminobutyric acid type B (GABA(B)) receptors mediate the transmi ssion of slow and prolonged inhibitory signals in the central nervous system, Two splice variants of GABA(B) receptors, GABA(B)R1a and GABA( B)R1b, were recently cloned from a mouse cortical and cerebellar cDNA library. As predicted, these receptors belong to the G protein-coupled receptor superfamily. We have used epitope-tagged versions of GABA(B) R1a receptors to study the cellular distribution of these proteins in a variety of non-neuronal and neuronal cell types. Here we report that recombinant GABA(B) receptors fail to reach the cell surface when exp ressed in heterologous systems and are retained in the endoplasmic ret iculum when introduced into COS cells. In addition, we prove that reco mbinant GABA(B) receptors are excluded from the cell surface when over expressed in ganglion neurons and we further demonstrate that they fai l to activate in superior cervical ganglion neurons. Together our obse rvations suggest that recombinant GABA(B) receptors require additional information for functional targeting to the plasma membrane.