C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(B) receptors

Assembly of fully functional GABA(B) receptors requires heteromerization of the GABA(B(1)) and GABA(B(2)) subunits. It is thought that GABA(B(1)) and GABA(B(2)) undergo coiled-coil dimerization in their cytoplasmic C termini and that assembly is necessary to overcome GABA(B(1)) retention in the endo plasmatic reticulum (ER). We investigated the mechanism underlying GABA(B(1 )) trafficking to the cell surface. We identified a signal, RSRR, proximal to the coiled-coil domain of GABA(B(1)) that when deleted or mutagenized al lows for surface delivery in the absence of GABA(B(2)). A similar motif, RX R, was recently shown to function as an ER retention/retrieval (ERR/R) sign al in K-ATP channels, demonstrating that G-protein-coupled receptors (GPCRs ) and ion channels use common mechanisms to control surface trafficking. A C-terminal fragment of GABA(B(2)) is able to mask the RSRR signal and to di rect the GABA(B(1)) monomer to the cell surface, where it is functionally i nert. This indicates that in the heteromer, GABA(B(2)) participates in coup ling to the G-protein. Mutagenesis of the C-terminal coiled-coil domains in GABA(B(1)) and GABA(B(2)) supports the possibility that their interaction is involved in shielding the ERR/R signal. However, assembly of heteromeric GABA(B) receptors is possible in the absence of the C-terminal domains, in dicating that coiled-coil interaction is not necessary for function. Rather than guaranteeing heterodimerization, as previously assumed, the coiled-co il structure appears to be important for export of the receptor complex fro m the secretory apparatus.