The gamma-aminobutyric acid type A receptor (GABA(A)R)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse

gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are ligand-gated chlor ide channels that exist in numerous distinct subunit combinations. At posts ynaptic membrane specializations. different GABA(A)R isoforms colocalize wi th the tubulin-binding protein gephyrin. However, direct interactions of GA BA(A)R subunits with gephyrin have not been reported. Recently, the GABA(A) R-associated protein GABARAP was found to bind to the gamma 2 subunit of GA BA(A)Rs. Here we show that GABARAP interacts with gephyrin in both biochemi cal assays and transfected cells. Confocal analysis of neurons derived from wild-type and gephyrin-knockout mice revealed that GABARAP is highly enric hed in intracellular compartments, but not at gephyrin-positive postsynapti c membrane specializations. Our data indicate that GABARAP-gephyrin interac tions are not important for postsynaptic GABA(A)R anchoring but may be impl icated in receptor sorting and/or targeting mechanisms. Consistent with thi s idea, a close homolog of GABARAP, p16, has been found to function as a la te-acting intra-Golgi transport factor.