Cell surface immobilization of GABAARs in cerebellar granule cells depends on the M3/M4 cytoplasmatic loop of the alpha 1 subunit

Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain. The localization of GABA receptors type A (GABAARs) at strategically located domains of the neuronal membrane is of vital importance for fast inhibitory synapse transmission efficacy. We have shown before that the lateral mobility of GABAARs depends on subunit composition of the complex. To study the lateral mobility of GABAARs in living, cultured neurons, we transfected cerebellar granule cells with either the complete 1 GABAAR subunit or with a truncation of the 1 subunit that lacks the major intracellular loop (M3/M4). We examined the location and lateral mobility of receptors containing both versions of the 1 subunit in living neurons. From fluorescence recovery after photobleaching experiments we present novel evidences that the intracellular M3/M4 loop of the 1 subunit restricts the lateral mobility of GABAARs when expressed in neurons. In addition, our immunocytochemical studies suggested that receptors containing the truncated subunit seem to be unable to reach synaptic localizations. Here we show for the first time that the 1 intracellular loop (M3/M4) domain has a relevant role in controlling the lateral mobility of GABAARs in neurons, and we believe that this is a novel and important contribution in neurobiology of GABAA receptors.