The 3'-untranslated region of CaMKII alpha is a cis-acting signal for the localization and translation of mRNA in dendrites
The 3'-untranslated region of CaMKII alpha is a cis-acting signal for the localization and translation of mRNA in dendrites
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DOI：
10.1073/pnas.93.23.13250
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Mayford, M;Baranes, D;Kandel, ER
神经元信号传导要求突触蛋白适当定位在细胞内并在那里受到调节。在哺乳动物神经元中，多核糖体不仅存在于细胞体中，而且还存在于树突中，它们集中在树突棘内部或下方。Ca2+-钙调蛋白依赖性蛋白激酶 II (CaMKII α) 的 α 亚基是仅有的五个亚基之一。 已知 mRNA 存在于树突以及神经元体中。 CaMKII α mRNA 的这种靶向亚细胞定位提供了一种可能的细胞生物学机制，既可以控制同源蛋白的分布，也可以独立调节单个树突棘中蛋白表达的水平。为了表征参与树突 mRNA 定位的顺式作用元件，我们产生了两个转基因小鼠品系，其中 CaMKII α 启动子用于驱动 lacZ 转录物的表达，该转录物包含或缺乏 CaMKII α 基因的 3'-非翻译区。尽管这两个小鼠系在前脑神经元中都显示出与内源性 CaMKII α 基因表达平行的表达，但只有带有 3'-非翻译区的 lacZ 转录物定位于树突，β-半乳糖苷酶蛋白在树突轴和树突棘内显示出不同的表达水平，这表明神经元可以控制树突的局部生物化学。 树突要么通过 mRNA 的差异定位，要么通过树突上不同位点翻译效率的变化。
Neuronal signaling requires that synaptic proteins be appropriately localized within the cell and regulated there, In mammalian neurons, polyribosomes are found not just in the cell body, but also in dendrites where they are concentrated within or beneath the dendritic spine, The alpha subunit of Ca2+-calmodulin-dependent protein kinase II (CaMKII alpha) is one of only five mRNAs known to be present within the dendrites, as well as in the soma of neurons. This targeted subcellular localization of the mRNA for CaMKII alpha provides a possible cell biological mechanism both for controlling the distribution of the cognate protein and for regulating independently the level of protein expression in individual dendritic spines. To characterize the cis-acting elements involved in the localization of dendritic mRNA we have produced two lines of transgenic mice in which the CaMKII alpha promoter is used to drive the expression of a lacZ transcript, which either contains or lacks the 3'-untranslated region of the CaMKII alpha gene. Although both lines of mice show expression in forebrain neurons that parallels the expression of the endogenous CaMKII alpha gene, only the lacZ transcripts bearing the 3'-untranslated region are localized to dendrites, The beta-galactosidase protein shows a variable level of expression along the dendritic shaft and within dendritic spines, which suggests that neurons can control the local biochemistry of the dendrite either through differential localization of the mRNA or variations in the translational efficiency at different sites along the dendrite.