The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors

GABA(A) receptors the major sites of fast synaptic inhibition in the brain are composed predominately of alpha, beta, and gamma2 subunits. The recepto r gamma2 subunit interacts with a 17-kDa microtubule associated protein GAB ARAP, but the significance of this interaction remains unknown. Here we dem onstrate that GABARAP, which immunoprecipitates with GABAA receptors, is no t found at significant levels within inhibitory synapses, but is enriched w ithin the Golgi apparatus and postsynaptic cisternae. We also demonstrate t hat GABARAP binds directly to N-ethylmaleimide-sensitive factor (NSF), a pr otein critical for intracellular membrane trafficking events. NSF and GABAR AP complexes could be detected in neurons and these two proteins also coloc alize within intracellular membrane compartments. Together our observations suggest that GABARAP may play a role in intracellular GABAA receptor trans port but not synaptic anchoring, via its ability to interact with NSF. GABA RAP may therefore have an important role in the production of GABAergic syn apses.