Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons

The majority of fast inhibitory synaptic transmission in the mammalian nervous system is mediated by GABA(A) receptors (GABA(A)Rs). Here we report a novel interaction between the protein Maf1 and GABA(A)R beta-subunit intracellular domains. We find Maf1 to be highly expressed in brain and enriched in the hippocampus and cortex. In heterologous cells and neurons we show Maf1 co-localises with GABA(A)Rs in intracellular compartments and at the cell surface. In neurons, Maf1 is found localised in the cytoplasm in dendrites, partially overlapping with GABA(A)Rs and inhibitory synapses and in addition is enriched in the neuronal nucleus. We also report that Maf1 interacts with a novel coiled-coil domain containing protein that we have called Macoco (for Maf1 interacting coiled-coil protein). Like Maf1, Macoco can also be found localised to inhibitory synapses and directly interacts with GABA(A)Rs. Expressing Macoco in neurons increases surface GABA(A)R levels. Our results suggest that Maf1 and Macoco are novel GABA(A)R interacting proteins important for regulating GABA(A)R surface expression and GABA(A)R signalling in the brain.