Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
J Cell Sci. 2013 Jan 1;126(Pt 1):90-102. doi: 10.1242/jcs.107268. Epub 2012 Oct 24.
Many neuronal mRNAs are transported from cell bodies into axons and dendrites. Localized translation of the mRNAs brings autonomy to these processes that can be vast distances from the cell body. For axons, these translational responses have been linked to growth and injury signaling, but there has been little information about local function of individual axonally synthesized proteins. In the present study, we show that axonal injury increases levels of the mRNA encoding neural membrane protein 35 (NMP35) in axons, with a commensurate decrease in the cell body levels of NMP35 mRNA. The 3' untranslated region (3'UTR) of NMP35 is responsible for this localization into axons. Previous studies have shown that NMP35 protein supports cell survival by inhibiting Fas-ligand-mediated apoptosis; however, these investigations did not distinguish functions of the locally generated NMP35 protein. Using axonally targeted versus cell-body-restricted NMP35 constructs, we show that NMP35 supports axonal growth, and overexpression of an axonally targeted NMP35 mRNA is sufficient to increase axonal outgrowth.
许多神经元 mRNA 从细胞体运输到轴突和树突。mRNA 的局部翻译为这些过程带来了自主性,这些过程可以远离细胞体。对于轴突,这些翻译反应与生长和损伤信号有关,但关于个体轴突合成蛋白的局部功能知之甚少。在本研究中,我们表明轴突损伤会增加编码神经膜蛋白 35(NMP35)的 mRNA 在轴突中的水平,同时细胞体中 NMP35 mRNA 的水平相应降低。NMP35 的 3'非翻译区(3'UTR)负责将其定位到轴突中。先前的研究表明,NMP35 蛋白通过抑制 Fas 配体介导的细胞凋亡来支持细胞存活;然而,这些研究没有区分局部产生的 NMP35 蛋白的功能。使用靶向轴突与局限于细胞体的 NMP35 构建体,我们表明 NMP35 支持轴突生长,并且过表达靶向轴突的 NMP35 mRNA 足以增加轴突生长。