Intracellular retention of recombinant GABAB receptors

gamma-Aminobutyric acid type B (GABA(B)) receptors mediate the transmission 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 expressed in heterologous systems and are retained in the endoplasmic reticulum when introduced into COS cells. In addition, we prove that recombinant GABA(B) receptors are excluded from the cell surface when overexpressed in ganglion neurons and we further demonstrate that they fail to activate in superior cervical ganglion neurons. Together our observations suggest that recombinant GABA(B) receptors require additional information for functional targeting to the plasma membrane.