McDonald B J, Amato A, Connolly C N, Benke D, Moss S J, Smart T G
MRC Laboratory for Molecular Cell Biology, University College, London, UK.
Nat Neurosci. 1998 May;1(1):23-8. doi: 10.1038/223.
Activation of cAMP-dependent protein kinase (PKA) can enhance or reduce the function of neuronal GABAA receptors, the major sites of fast synaptic inhibition in the brain. This differential regulation depends on PKA-induced phosphorylation of adjacent conserved sites in the receptor beta subunits. Phosphorylation of beta 3 subunit-containing receptors at S408 and S409 enhanced the GABA-activated response, whereas selectively mutating S408 to alanine converted the potentiation into an inhibition, comparable to that of beta 1 subunits, which are phosphorylated solely on S409. These distinct modes of regulation were interconvertible between beta 1 and beta 3 subunits and depended upon the presence of S408 in either subunit. In contrast, beta 2 subunit-containing receptors were not phosphorylated or affected by PKA. Differential regulation by PKA of postsynaptic GABAA receptors containing different beta subunits may have profound effects on neuronal excitability.
环磷酸腺苷依赖性蛋白激酶（PKA）的激活可增强或降低神经元γ-氨基丁酸A型（GABAA）受体的功能，该受体是大脑中快速突触抑制的主要位点。这种差异调节取决于PKA诱导的受体β亚基中相邻保守位点的磷酸化。含β3亚基的受体在S408和S409处的磷酸化增强了γ-氨基丁酸（GABA）激活的反应，而将S408选择性地突变为丙氨酸则将增强作用转变为抑制作用，这与仅在S409处磷酸化的β1亚基的抑制作用相当。这些不同的调节模式在β1和β3亚基之间是可相互转换的，并且取决于任一亚基中S408的存在。相比之下，含β2亚基的受体不会被PKA磷酸化或受其影响。PKA对含有不同β亚基的突触后GABAA受体的差异调节可能对神经元兴奋性产生深远影响。
