Modulation of cell surface GABA(B) receptors by desensitization, trafficking and regulated degradation.

Inhibitory neurotransmission ensures normal brain function by counteracting and integrating excitatory activity. γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system, and mediates its effects via two classes of receptors: the GABA(A) and GABA(B) receptors. GABA(A) receptors are heteropentameric GABA-gated chloride channels and responsible for fast inhibitory neurotransmission. GABA(B) receptors are heterodimeric G protein coupled receptors (GPCR) that mediate slow and prolonged inhibitory transmission. The extent of inhibitory neurotransmission is determined by a variety of factors, such as the degree of transmitter release and changes in receptor activity by posttranslational modifications (e.g., phosphorylation), as well as by the number of receptors present in the plasma membrane available for signal transduction. The level of GABA(B) receptors at the cell surface critically depends on the residence time at the cell surface and finally the rates of endocytosis and degradation. In this review we focus primarily on recent advances in the understanding of trafficking mechanisms that determine the expression level of GABA(B) receptors in the plasma membrane, and thereby signaling strength.