Nakamura Yasuko, Darnieder Laura M, Deeb Tarek Z, Moss Stephen J
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Adv Pharmacol. 2015;72:97-146. doi: 10.1016/bs.apha.2014.11.008. Epub 2014 Dec 19.
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.
γ-氨基丁酸A型受体（GABAARs）是大脑中快速突触抑制以及低持续性突触外抑制的主要介质，这两者对于大脑的正常功能都至关重要。因此，毫不奇怪，GABAARs的缺陷与许多神经系统疾病有关。GABAAR调节的复杂性不仅取决于这些受体的异质性，还取决于其翻译后修饰，其中最重要且特征最明显的是磷酸化。本综述将探讨这一动态过程的细节，我们对其的了解还只是皮毛。GABAARs受多种激酶和磷酸酶的调节，其磷酸化在控制其转运、表达和相互作用伙伴方面起着重要作用。在这里，我们总结了在理解磷酸化在GABAARs调节中所起作用方面取得的进展。这包括磷酸化如何影响GABAARs的变构调节，以及影响GABAAR磷酸化的信号通路。最后，我们讨论了GABAAR磷酸化的失调及其在疾病过程中的意义。
