International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
J Neurosci. 2011 Apr 6;31(14):5271-85. doi: 10.1523/JNEUROSCI.2387-10.2011.
The pattern of dendritic branching, together with the density of synapses and receptor composition, defines the electrical properties of a neuron. The development of the dendritic arbor and its additional stabilization are highly orchestrated at the molecular level and are guided by intrinsic mechanisms and extracellular information. Although protein translation is known to contribute to these processes, the role of its local component has not been fully explored. For local translation, mRNAs are transported to dendrites in their dormant form as ribonucleoparticles (RNPs). We hypothesized that disturbing spatial mRNA distribution via RNP targeting may result in severe underdevelopment of the dendritic arbor. Zipcode binding protein 1 (ZBP1) controls β-actin mRNA transport and translation in dendrites. We showed that proper cellular levels of ZBP1, its ability to engage in mRNA binding, and Src-dependent release of mRNA cargo from ZBP1 are vital for dendritic arbor development in cultured rat hippocampal neurons. Moreover, β-actin overexpression significantly alleviated the effects of ZBP1 knockdown. These results suggest that ZBP1-dependent dendritic mRNA transport contributes to proper dendritic branching.
树突分支的模式，加上突触密度和受体组成，决定了神经元的电特性。树突树突的发育及其额外的稳定在分子水平上是高度协调的，受内在机制和细胞外信息的指导。尽管已知蛋白质翻译对这些过程有贡献，但局部成分的作用尚未得到充分探索。对于局部翻译，mRNA 以核糖核蛋白 (RNP) 的休眠形式运输到树突中。我们假设，通过 RNP 靶向干扰空间 mRNA 分布可能导致树突严重发育不良。Zipcode 结合蛋白 1 (ZBP1) 控制β-肌动蛋白 mRNA 在树突中的运输和翻译。我们表明，ZBP1 的适当细胞水平、其与 mRNA 结合的能力以及Src 依赖性从 ZBP1 释放 mRNA 货物对于培养的大鼠海马神经元中的树突发育至关重要。此外，β-肌动蛋白过表达显著缓解了 ZBP1 敲低的影响。这些结果表明，ZBP1 依赖性树突 mRNA 运输有助于适当的树突分支。
