The γ-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the svnapse

摘要

γ-Aminobutyric acid type A receptors (GABAARs) are ligand-gated chloride channels that exist in numerous distinct subunit combi- nations. At postsynaptic membrane specializations. different GABAAR isoforms colocalize with the tubulin-binding protein gephyrin. However, direct interactions of GABAAR subunits with gephyrin have not been reported. Recently. the GABAAR-associ- ated protein GABARAP was found to bind to the γ2 subunit of GABAARs. Here we show that GABARAP interacts with gephyrin in both biochemical assays and transfected cells. Confocal analysis of neurons derived from wild-type and gephyrin-knockout mice re- vealed that GABARAP is highly enriched in intracellular compart- ments. but not at gephyrin-positive postsynaptic membrane specializations. Our data indicate that GABARAP--gephyrin inter- actions are not important for postsynaptic GABAAR anchoring but may be implicated in receptor sorting and/or targeting mecha- nisms. Consistent with this idea. a close homolog of GABARAP, p16, has been found to function as a late-acting intra-Golgi transport factor.