A trafficking checkpoint controls GABA(B) receptor heterodimerization.
Surface expression of GABA(B) receptors requires heterodimerization of GB1 and GB2 subunits, but little is known about mechanisms that ensure efficient heterodimer assembly. We found that expression of the GB1 subunit on the cell surface is prevented through a C-terminal retention motif RXR(R); this sequence is reminiscent of the ER retention/retrieval motif RKR identified in subunits of the ATP-sensitive K+ channel. Interaction of GB1 and GB2 through their C-terminal coiled-coil alpha helices masks the retention signal in GB1, allowing the plasma membrane expression of the assembled complexes. Because individual GABA(B) receptor subunits and improperly assembled receptor complexes are not functional even if expressed on the cell surface, we conclude that a trafficking checkpoint ensures efficient assembly of functional GABA(B) receptors.
Margeta-Mitrovic
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Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D004594:Electrophysiology; D019085:Fluorescent Antibody Technique, Direct; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008565:Membrane Proteins / Q000378:metabolism; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D018080:Receptors, GABA-B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014981:Xenopus
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008565:Membrane Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018080:Receptors, GABA-B