Calcium/calmodulin-dependent kinase II phosphorylation of the GABAA receptor α1 subunit modulates benzodiazepine binding
Calcium/calmodulin-dependent kinase II phosphorylation of the GABAA receptor α1 subunit modulates benzodiazepine binding
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DOI：
10.1046/j.1471-4159.2002.01032.x
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发表时间：
2002-09-01
影响因子：
4.7
通讯作者：
Delorenzo, RJ
中科院分区：
文献类型：
--
作者：
Churn, SB;Rana, A;Delorenzo, RJ
γ-氨基丁酸（GABA）是中枢神经系统中负责快速抑制性突触传递的主要神经递质。能够快速调节GABA（A）R功能的主要翻译后机制是受体磷酸化。本研究旨在检测内源性钙和钙调素依赖性激酶II（CaM激酶II）激活对变构调节剂结合和GABA（A）受体亚基磷酸化的影响。刺激内源性CaM激酶II活性，随后分析GABA（A）受体的两种别构调节剂结合特性，并免疫沉淀和分析亚基磷酸化水平。在CaM激酶II激活最大的条件下，观察到GABA（A）R的变构调节剂结合显著增加。此外，CaM激酶II激活导致GABA（A）受体α 1亚基磷酸化的直接增加。这些数据表明，GABA（A）受体α 1亚基的CaM激酶II依赖性磷酸化调节了与GABA（A）受体结合的变构调节剂。
gamma-Aminobutyric acid (GABA) is the primary neurotransmitter that is responsible for the fast inhibitory synaptic transmission in the central nervous system. A major post-translational mechanism that can rapidly regulate GABA(A) R function is receptor phosphorylation. This study was designed to test the effect of endogenous calcium and calmodulin-dependent kinase II (CaM kinase II) activation on both allosteric modulator binding and GABA(A) receptor subunit phosphorylation. Endogenous CaM kinase II activity was stimulated, and GABA(A) receptors were subsequently analyzed for bothallosteric modulator binding properties and immunoprecipitated and analyzed for subunit phosphorylation levels. A significant increase in allosteric-modulator binding of the GABA(A) R was observed under conditions maximal for CaM kinase II activation. In addition, CaM kinase II activation resulted in a direct increase in phosphorylation of the GABA(A) receptor alpha1 subunit. The data suggest that the CaM kinase II-dependent phosphorylation of the GABA(A) receptor alpha1 subunit modulated allosteric modulator binding to the GABA(A) receptor.