Association of GRIP1 with a GABAA receptor associated protein suggests a role for GRIP1 at inhibitory synapses

GABA(A) receptors mediate the majority of fast synaptic inhibition in the mammalian central nervous system. GABA(A) receptors associate with a number of cytosolic proteins important for regulating their function including the GABA(A) receptor gamma2 subunit associated protein GABARAP. Here we show GABARAP associates with the synaptic PDZ domain containing protein GRIP1. GRIP1 has been localized to inhibitory synapses however the role of this protein with respect to neuronal inhibition remains unclear. Using in vitro protein interaction assays we show that GABARAP interacts directly with PDZ domains 4-6 of GRIP1. Furthermore, using coimmunoprecipitation assays we show that GABARAP interacts with GRIP1 in vivo. Finally, we show that GRIP1 colocalizes with gamma2 subunit containing GABA(A) receptors in cultured hippocampal neurons. Our findings provide evidence that GRIP1 can associate with proteins important for regulating GABA(A) receptor function and suggest that GRIP1 may play a role at inhibitory synapses. (C) 2004 Elsevier Inc. All rights reserved.