Figure 5.
Ubiquitination at inhibitory synapses. At inhibitory synapses, ubiquitination of the γ2 subunit of GABAA receptors (GABAARs) results in lysosomal degradation of GABAARs. Binding of Plic-1 to GABAARs in the endoplasmic reticulum (ER) leads to stabilization of ubiquitinated GABAARs and promotes their forward trafficking. Interactions of GABAAR with the ubiquitin-like proteins GABARAP and Plic-1 promote recycling and aid in postsynaptic clustering of GABAARs. Interactions of GABARAP with GRIP-1 further aid in the clustering of postsynaptically expressed GABAARs. Ubiquitination and destabilization of GABAARs in the ER are accelerated by Ca2+ signaling through L-type voltage-gated calcium channels (VGCCs) by an unknown ubiquitin E3 ligase. EE, early endosome; LE, late endosome; RE, recycling endosome.