Abstract

GABAB receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Whereas heterodimerization between GABAB receptor GABABR1 and GABABR2 subunits is essential for functional expression, how neurons coordinate the assembly of these critical receptors remains to be established. Here we have identified Marlin-1, a novel GABAB receptor-binding protein that associates specifically with the GABABR1 subunit in yeast, tissue culture cells, and neurons. Marlin-1 is expressed in the brain and exhibits a granular distribution in cultured hippocampal neurons. Marlin-1 binds different RNA species including the 3?-untranslated regions of both the GABABR1 and GABABR2 mRNAs in vitro and also associates with RNA in cultured neurons. Inhibition of Marlin-1 expression via small RNA interference technology results in enhanced intracellular levels of the GABABR2 receptor subunit without affecting the level of GABA BR1. Together our results suggest that Marlin-1 functions to regulate the cellular levels of GABAB R2 subunits, which may have significant effects on the production of functional GABAB receptor heterodimers. Therefore, our observations provide an added level of regulation for the control of GABAB receptor expression and for the efficacy of inhibitory synaptic transmission.