Ingi T, Krumins A M, Chidiac P, Brothers G M, Chung S, Snow B E, Barnes C A, Lanahan A A, Siderovski D P, Ross E M, Gilman A G, Worley P F
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21210, USA.
J Neurosci. 1998 Sep 15;18(18):7178-88. doi: 10.1523/JNEUROSCI.18-18-07178.1998.
Long-term neuronal plasticity is known to be dependent on rapid de novo synthesis of mRNA and protein, and recent studies provide insight into the molecules involved in this response. Here, we demonstrate that mRNA encoding a member of the regulator of G-protein signaling (RGS) family, RGS2, is rapidly induced in neurons of the hippocampus, cortex, and striatum in response to stimuli that evoke plasticity. Although several members of the RGS family are expressed in brain with discrete neuronal localizations, RGS2 appears unique in that its expression is dynamically responsive to neuronal activity. In biochemical assays, RGS2 stimulates the GTPase activity of the alpha subunit of Gq and Gi1. The effect on Gi1 was observed only after reconstitution of the protein in phospholipid vesicles containing M2 muscarinic acetylcholine receptors. RGS2 also inhibits both Gq- and Gi-dependent responses in transfected cells. These studies suggest a novel mechanism linking neuronal activity and signal transduction.
已知长期神经元可塑性依赖于mRNA和蛋白质的快速从头合成,最近的研究深入探讨了参与这种反应的分子。在这里,我们证明,编码G蛋白信号调节剂(RGS)家族成员RGS2的mRNA在海马体、皮质和纹状体的神经元中,对诱发可塑性的刺激做出快速诱导反应。尽管RGS家族的几个成员在大脑中具有离散的神经元定位表达,但RGS2显得独特,因为其表达对神经元活动具有动态反应。在生化分析中,RGS2刺激Gq和Gi1的α亚基的GTP酶活性。只有在含有M2毒蕈碱型乙酰胆碱受体的磷脂囊泡中重组该蛋白后,才观察到对Gi1的影响。RGS2还抑制转染细胞中Gq和Gi依赖性反应。这些研究提示了一种将神经元活动与信号转导联系起来的新机制。