Mohr E, Richter D
Institute for Cell Biochemistry and Clinical Neurobiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
J Neuroendocrinol. 2004 Apr;16(4):333-9. doi: 10.1111/j.0953-8194.2004.01176.x.
Vasopressin mRNA is delivered to axons and dendrites of rat hypothalamic magnocellular neurones. Subcellular localization of mRNAs requires sequences (cis-acting elements) within the RNA and proteins (trans-acting factors), which together mediate nucleic acid transport along the cytoskeleton to specific cytoplasmic destinations. In cultured neurones, vasopressin mRNA transcribed from a microinjected eukaryotic expression vector is sorted to dendrites. Detailed analyses revealed the presence of a complex cis-acting element, called dendritic localizer sequence (DLS), within part of the coding- and the 3'-untranslated region of vasopressin mRNA. Biochemical investigations have shown a specific interaction of poly(A)-binding protein (PABP) with the DLS. PABP is implicated in translation, translational control, RNA stability and RNA transport. Hence, PABP could be a component of a probably multifactor complex regulating transport and local translation of vasopressin mRNA. Dendrites are capable of translation. Local synthesis of the vasopressin precursor in dendrites of in vitro cultured neurones was demonstrated by microinjecting a vector encoding a mutant vasopressin polyprotein that is unable to leave the rough endoplasmic reticulum. Expression of this construct revealed that the nondiffusable protein is only detectable in dendrites harbouring vasopressin mRNA whereas dendrites devoid of this transcript lack the mutant vasopressin precursor.
血管加压素信使核糖核酸被运送到大鼠下丘脑大细胞神经元的轴突和树突。信使核糖核酸的亚细胞定位需要核糖核酸内的序列（顺式作用元件）和蛋白质（反式作用因子），它们共同介导核酸沿着细胞骨架运输到特定的细胞质目的地。在培养的神经元中，从显微注射的真核表达载体转录的血管加压素信使核糖核酸被分选到树突中。详细分析显示，在血管加压素信使核糖核酸的部分编码区和3'非翻译区内存在一种复杂的顺式作用元件，称为树突定位序列（DLS）。生化研究表明，多聚腺苷酸结合蛋白（PABP）与DLS存在特异性相互作用。PABP与翻译、翻译控制、核糖核酸稳定性及核糖核酸运输有关。因此，PABP可能是调节血管加压素信使核糖核酸运输和局部翻译的多因子复合物的一个组成部分。树突能够进行翻译。通过显微注射编码一种无法离开粗面内质网的突变型血管加压素多蛋白的载体，证明了体外培养神经元树突中血管加压素前体的局部合成。表达该构建体显示，不可扩散的蛋白仅在含有血管加压素信使核糖核酸的树突中可检测到，而缺乏该转录本的树突则没有突变型血管加压素前体。
