RNA editing of the serotonin 2C receptor and expression of Galpha(q) protein: genetic mouse models do not support a role for regulation or compensation.

RNA editing of the serotonin 2C receptor and expression of Galpha(q) protein: genetic mouse models do not support a role for regulation or compensation.
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DOI:
10.1111/j.1471-4159.2008.05852.x
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发表时间:
2009-03
影响因子:
4.7
通讯作者:
Airey DC
Airey DC
中科院分区:
医学2区
文献类型:
--
作者:
Canal CE;Mahautmr KC;Cao C;Sanders-Bush E;Airey DC

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5-HT2C(5-HT2C)受体在编码第二细胞内环的前mRNA区域的5个碱基上经历RNA编辑,产生许多独特的5-HT2C受体亚型。不同编辑的5-HT2C受体亚型在体内表达的调节机制尚不清楚,编辑特征变化的适应性后果也是如此。最近的研究结果表明,G-αQ/11蛋白的表达水平与5-HT2C受体转录本的编辑程度之间可能存在关系。为了阐明GαQ/11蛋白水平的潜在调节或适应作用,我们量化了GαQ缺失小鼠5-HT2C受体转录本的编辑,以及仅表达5-HT2C受体的未编辑(INI)或完全编辑(VGV)亚型的转基因雄性小鼠中GαQ和Gα11的蛋白水平。对G、α、Q缺失型和野生型小鼠杏仁核皮质的5-HT2C受体基因编辑图谱进行焦磷酸测序,结果显示差异不显著。用Western blotting检测INI/y、VGV/y和野生型小鼠大脑皮质GαQ和Gα11亚单位的表达。野生型与INI/y或VGV/y组之间信号密度无差异,表明GαQ和Gα11蛋白的表达水平相当。总之,这些数据不支持5-HT2C受体RNA编辑和GQ蛋白水平之间的因果或补偿关系。
The serotonin 2C (5-HT2C) receptor undergoes RNA editing at five bases in a region of the pre-mRNA encoding the second intracellular loop, generating many unique 5-HT2C receptor isoforms. Mechanisms regulating in vivo expression of different edited 5-HT2C receptor isoforms are poorly understood, as are the adaptive consequences of variation in editing profiles. Recent findings suggest a putative relationship between expression levels of Gαq/11 protein and the degree of editing of 5-HT2C receptor transcripts. To elucidate the potential regulatory or adaptive role of Gαq/11 protein levels, we quantified editing of 5-HT2C receptor RNA transcripts in Gαq null mice and protein levels of Gαq and Gα11 in transgenic male mice solely expressing either the non-edited (INI) or the fully edited (VGV) isoforms of the 5-HT2C receptor. Pyrosequencing of RNA isolated from amygdaloid cortex in Gαq null and wild-type mice revealed no significant differences in 5-HT2C receptor mRNA editing profiles. Cortical tissue from INI/y, VGV/y, and wild-type mice was assayed for expression of Gαq and Gα11 subunits by Western blotting. No differences in signal density between wild-type and INI/y or VGV/y groups were found, indicating equivalent levels of Gαq and Gα11 protein. Together, these data do not support a causal or compensatory relationship between 5-HT2C receptor RNA editing and Gq protein levels.
DOI: 10.1046/j.1471-4159.1999.731711.x
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