Functional modulation of GABAB receptors by protein kinases and receptor trafficking.

Advances in Pharmacology
Miho TerunumaStephen J Moss

Abstract

GABA(B) receptors (GABA(B)R) are heterodimeric G protein-coupled receptors (GPCRs) that mediate slow and prolonged inhibitory signals in the central nervous system. The signaling of GPCRs is under stringent control and is subject to regulation by multiple posttranslational mechanisms. The beta-adrenergic receptor is a prototypic GPCR. Like most GPCRs, prolonged exposure of this receptor to agonist induces phosphorylation of multiple intracellular residues that is largely dependent upon the activity of G protein-coupled receptor kinases (GRKs). Phosphorylation terminates receptor-effector coupling and promotes both interaction with beta-arrestins and removal from the plasma membrane via clathrin-dependent endocytosis. Emerging evidence for GABA(B)Rs suggests that these GPCRs do not conform to this mode of regulation. Studies using both native and recombinant receptor preparations have demonstrated that GABA(B)Rs do not undergo agonist-induced internalization and are not GRK substrates. Moreover, whilst GABA(B)Rs undergo clathrin-dependent constitutive endocytosis, it is generally accepted that their rates of internalization are not modified by prolonged agonist exposure. Biochemical studies have revealed that GABA(B)Rs are phosp...Continue Reading

Citations

Apr 23, 2015·Cellular and Molecular Life Sciences : CMLS·Karim NagiGraciela Pineyro
Dec 14, 2018·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Miho Terunuma
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Feb 23, 2020·Journal of Neurochemistry·Mohammad I K HamadEckart Förster
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Jul 21, 2017·FEBS Letters·Uri KahanovitchNathan Dascal
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