PNUTS forms a trimeric protein complex with GABA(C) receptors and protein phosphatase 1

Phosphorylation and dephosphorylation of neurotransmitter receptors represent an important mechanism to regulate synaptic signal transduction. Here, we identified PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding partner of GABA_C receptors. In the mammalian retina, PNUTS is co-expressed with GABA_C receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in membrane protein preparations of the retina and precipitate with GABA_C receptor specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane in cells co-expressing GABA_C receptors. We show simultaneous binding of PP1 and GABA_C receptors to different domains of PNUTS, demonstrating that PNUTS cross-links PP1 and GABA_C receptors. Finally, modeling studies showed that the PP1 docking motif of PNUTS fits into the binding pocket on the enzyme surface, despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to synaptic sites, acting as a temporary bridge between the phosphatase and GABA_C receptors.