Sotelo-Silveira Jose R, Calliari Aldo, Kun Alejandra, Koenig Edward, Sotelo Jose R
Department of Proteins and Nucleic Acids, Instituto de Investigaciones Biologicas Clemente Estable, Montevideo, Uruguay.
Traffic. 2006 May;7(5):508-15. doi: 10.1111/j.1600-0854.2006.00405.x.
A substantial number of studies over a period of four decades have indicated that axons contain mRNAs and ribosomes, and are metabolically active in synthesizing proteins locally. For the most part, little attention has been paid to these findings until recently when the concept of targeting of specific mRNAs and translation in subcellular domains in polarized cells emerged to contribute to the likelihood and acceptance of mRNA targeting to axons as well. Trans-acting factor proteins bind to cis-acting sequences in the untranslated region of mRNAs integrated in ribonucleoprotein (RNPs) complexes determine its targeting in neurons. In vitro studies in immature axons have shown that molecular motors proteins (kinesins and myosins) associate to RNPs suggesting they would participate in its transport to growth cones. Tau and actin mRNAs are transported as RNPs, and targeted to axons as well as ribosomes. Periaxoplasmic ribosomal plaques (PARPs), which are systematically distributed discrete peripheral ribosome-containing, actin-rich formations in myelinated axons, also are enriched with actin and myosin Va mRNAs and additional regulatory proteins. The localization of mRNAs in PARPs probably means that PARPs are local centers of translational activity, and that these domains are the final destination in the axon compartment for targeted macromolecular traffic originating in the cell body. The role of glial cells as a potentially complementary source of axonal mRNAs and ribosomes is discussed in light of early reports and recent ultrastructural observations related to the possibility of glial-axon trans-endocytosis.
在四十年的时间里,大量研究表明轴突含有信使核糖核酸(mRNA)和核糖体,并且在局部合成蛋白质方面具有代谢活性。在很大程度上,直到最近,当极化细胞中亚细胞结构域中特定mRNA靶向和翻译的概念出现,使得mRNA靶向轴突的可能性和认可度增加时,这些发现才受到较少关注。反式作用因子蛋白与整合在核糖核蛋白(RNP)复合物中的mRNA非翻译区的顺式作用序列结合,决定其在神经元中的靶向。对未成熟轴突的体外研究表明,分子马达蛋白(驱动蛋白和肌球蛋白)与核糖核蛋白相关联,表明它们会参与其向生长锥的运输。Tau和肌动蛋白mRNA作为核糖核蛋白被运输,并靶向轴突以及核糖体。轴周核糖体斑块(PARP)是有髓轴突中系统分布的离散外周含核糖体、富含肌动蛋白的结构,也富含肌动蛋白和肌球蛋白Va mRNA以及其他调节蛋白。mRNA在PARP中的定位可能意味着PARP是翻译活性的局部中心,并且这些结构域是源自细胞体的靶向大分子运输在轴突区室中的最终目的地。根据早期报告和最近与胶质细胞 - 轴突转胞吞作用可能性相关的超微结构观察,讨论了胶质细胞作为轴突mRNA和核糖体潜在补充来源的作用。