The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx
The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx
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DOI：
10.1073/pnas.240452197
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发表时间：
2000-12-05
影响因子：
11.1
通讯作者：
Marshall, FH
中科院分区：
文献类型：
--
作者：
White, JH;McIllhinney, RA;Marshall, FH
γ-氨基丁酸B型（GABA（B））受体介导抑制性神经递质GABA的代谢作用。已知这些七跨膜受体主要通过激活G蛋白来调节离子通道或第二信使的作用而发出信号。功能性GABA（B）受体由异源二聚体组成，所述异源二聚体由两个亚基GABA（B）-R1和GABA（B）-R2组成，所述两个亚基通过其C末端尾部中的卷曲螺旋结构域相互作用。通过酵母双杂交方法，我们鉴定了GABA（B）-R1和GABA（B）-R2的C-末端尾部与两个相关转录因子CREB 2（ATF 4）和ATFx之间的直接相互作用。在原代神经元培养物以及表达GABA（B）受体的重组中国仓鼠卵巢细胞中，CREB 2定位于细胞质以及细胞核内。通过特异性激动剂巴氯芬激活GABAB受体导致CREB 2从细胞质到细胞核的显著易位和积累。我们证明，受体刺激的结果从CREB 2响应报告基因的转录激活。这种信号传导机制在家族C C蛋白偶联受体中是独特的，并且在GABA（B）受体和CREB 2的情况下，可能在神经系统的长期变化中起作用。
gamma -Aminobutyric acid type B (GABA(B)) receptors mediate the metabotropic actions of the inhibitory neurotransmitter GABA. These seven-transmembrane receptors are known to signal primarily through activation of G proteins to modulate the action of ion channels or second messengers. The functional GABA(B) receptor is made up of a heterodimer consisting of two subunits, GABA(B)-R1 and GABA(B)-R2, which interact via coiled-coil domains in their C-terminal tails. By using a yeast two-hybrid approach, we have identified direct interactions between the C-terminal tails of GABA(B)-R1 and GABA(B)-R2 with two related transcription factors, CREB2 (ATF4) and ATFx. In primary neuronal cultures as well in recombinant Chinese hamster ovary cells expressing GABA(B) receptors, CREB2 is localized within the cytoplasm as well as the nucleus. Activation of the GABAB receptor by the specific agonist baclofen leads to a marked translocation and accumulation of CREB2 from the cytoplasm into the nucleus. We demonstrate that receptor stimulation results in activation of transcription from a CREB2 responsive reporter gene. Such a signaling mechanism is unique among Family C C protein-coupled receptors and, in the case of the GABA(B) receptor and CREB2, may play a role in long-term changes in the nervous system.