Figure 2.

GABA_B receptor interacting proteins. A number of proteins have been found to interact with the C-terminus of GABA_B receptor subunits. Among the interacting proteins are leucine-zipper transcription factors ATF4/CREB2 and CHOP, scaffolding and adaptor proteins 14-3-3, GISP, NSF, and PDZ domain-containing scaffold proteins Shrm4 and Mupp1. It is proposed that these proteins regulate receptor dimerization, intracellular trafficking, and synaptic localization. The C-terminus of the R2 subunit associates with KCTD proteins, which regulate Ca_V channel activity and GABA_B receptor trafficking. The C-terminus of the R1 subunit associates with the brain-specific RNA binding protein Marlin-1 to target the cytoskeleton and regulate receptor transportation. Neurotransmitter receptors such as GABA_A receptor γ2 subunit, mGluRs, and GIRK channels are also GABA_B receptor binding partners although only the γ2 subunit has been identified to directly associate with R1 subunits so far. The N-terminus of R1 subunits also interact with proteins such as extracellular matrix protein fibulin-2 and tenascin. The extracellular sushi domains of the R1 subunit interact with fibulin-2, whereas tenascin binds to the extracellular domains of R1 subunits, possibly via the second transmembrane domain. Other proteins such as Gi/o proteins and RGS proteins bind to the R2 subunit to induce GPCR signaling.