Figure 2.
GABAA receptor trafficking. GABAA receptors are synthesized and assembled in the Endoplasmic Reticulum and matured in the Golgi and reach the surface outside of synapses through the secretory path. Synaptic receptors reach their destination through lateral movement in the plasma membrane, where they mediate phasic inhibition. Extrasynaptic receptors are activated by lower concentrations of GABA in the extracellular space and mediate tonic inhibition. Phosphorylation not only affects receptor function, but also regulates their removal from the surface through clathrin mediated endocytosis. From the endosomal system the receptors are either recycled to the surface or degraded in the lysosomes. This degradation can be blocked by leupeptin. Another degradation system works through the proteasome after ubiquitylation.