Modulation of cell surface GABAB receptors by desensitization, trafficking and regulated degradation

Figure 2 Mechanisms of GABA_B receptor desensitization. Three distinct mechanisms have been so far implicated in the desensitization of GABA_B receptors. In cerebellar granule cells, G protein receptor kinase (GRK) 4 and 5 associate with GABA_B receptors and induce desensitization of the receptors in a phosphorylation-independent manner. In cortical and hippocampal neurons, desensitization of the receptors involves the interaction of NEM-sensitive fusion protein (NSF) with GABA_B1 and GABA_B2, which is thought to prime the receptor for phosphorylation by protein kinase C (PKC). Association of potassium channel tetramerization domain-containing (KCTD) proteins 12 and 12b with the C-terminus of GABA_B2 appears to render the receptor complex competent for desensitization. GABA: γ-Aminobutyric acid.