title: Regulation of GABAARs by phosphorylation.
abstract: γ-Aminobutyric acid type A receptors (GABAARs) are the principal mediators of fast synaptic inhibition in the brain as well as the low persistent extrasynaptic inhibition, both of which are fundamental to proper brain function. Thus unsurprisingly, deficits in GABAARs are implicated in a number of neurological disorders and diseases. The complexity of GABAAR regulation is determined not only by the heterogeneity of these receptors but also by its posttranslational modifications, the foremost, and best characterized of which is phosphorylation. This review will explore the details of this dynamic process, our understanding of which has barely scratched the surface. GABAARs are regulated by a number of kinases and phosphatases, and its phosphorylation plays an important role in governing its trafficking, expression, and interaction partners. Here, we summarize the progress in understanding the role phosphorylation plays in the regulation of GABAARs. This includes how phosphorylation can affect the allosteric modulation of GABAARs, as well as signaling pathways that affect GABAAR phosphorylation. Finally, we discuss the dysregulation of GABAAR phosphorylation and its implication in disease processes.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Darnieder
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Tarek Z
authors.initials: TZ
authors.lastname: Deeb
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA. Electronic address: stephen.moss@tufts.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009422:Nervous System Diseases / Q000503:physiopathology*; D010766:Phosphorylation / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A
keywords: CamKII; GABA; GABA(A) receptor; Inhibitory synapse; Kinase; PKA; PKC; Phosphatase; Phosphorylation; Src