Regulation of GABAARs by phosphorylation.
Regulation of GABAARs by phosphorylation.
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DOI：
10.1016/bs.apha.2014.11.008
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Moss SJ
中科院分区：
文献类型：
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作者：
Nakamura Y;Darnieder LM;Deeb TZ;Moss SJ
γ-氨基丁酸A型受体（γ-Aminobutyric acid type A receptor，GABAARs）是脑内快速突触抑制和低持续性突触外抑制的主要介质，两者都是正常脑功能的基础。因此，GABAAR的缺陷与许多神经障碍和疾病有关，这并不令人惊讶。GABAAR调控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，最重要的和最具特征的是磷酸化。这篇评论将探讨这个动态过程的细节，我们对它的理解几乎没有触及表面。GABAAR受多种激酶和磷酸酶的调节，其磷酸化在调控其运输、表达和相互作用伙伴中起重要作用。本文就磷酸化在GABAARs调控中的作用进行综述。这包括磷酸化如何影响GABAAR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。
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.