Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0683, USA.
Mol Biol Cell. 2011 Nov;22(21):4038-46. doi: 10.1091/mbc.E10-07-0572. Epub 2011 Aug 31.
The unique architecture of neurons requires the establishment and maintenance of polarity, which relies in part on microtubule-based transport to deliver essential cargo into dendrites. To test different models of differential motor protein regulation and to understand how different compartments in neurons are supplied with necessary functional proteins, we studied mechanisms of dendritic transport, using Drosophila as a model system. Our data suggest that dendritic targeting systems in Drosophila and mammals are evolutionarily conserved, since mammalian cargoes are moved into appropriate domains in Drosophila. In a genetic screen for mutants that mislocalize the dendritic marker human transferrin receptor (hTfR), we found that kinesin heavy chain (KHC) may function as a dendritic motor. Our analysis of dendritic and axonal phenotypes of KHC loss-of-function clones revealed a role for KHC in maintaining polarity of neurons, as well as ensuring proper axonal outgrowth. In addition we identified adenomatous polyposis coli 1 (APC1) as an interaction partner of KHC in controlling directed transport and modulating kinesin function in neurons.
神经元的独特结构需要建立和维持极性，这部分依赖于基于微管的运输，将必要的货物运送到树突中。为了测试不同的差异运动蛋白调节模型，并了解神经元的不同隔室如何供应必要的功能蛋白，我们使用果蝇作为模型系统研究了树突运输的机制。我们的数据表明，果蝇和哺乳动物的树突靶向系统在进化上是保守的，因为哺乳动物的货物被运送到果蝇中的适当区域。在一个针对错误定位树突标记人转铁蛋白受体 (hTfR) 的突变体的遗传筛选中，我们发现驱动蛋白重链 (KHC) 可能作为树突马达发挥作用。我们对 KHC 功能丧失克隆的树突和轴突表型的分析表明，KHC 在维持神经元极性以及确保正确的轴突生长方面发挥作用。此外，我们还确定腺瘤性结肠息肉病基因 1 (APC1) 是 KHC 的相互作用伙伴，可控制定向运输并调节神经元中的驱动蛋白功能。
