A role for kinesin heavy chain in controlling vesicle transport into dendrites in Drosophila.
A role for kinesin heavy chain in controlling vesicle transport into dendrites in Drosophila.
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DOI：
10.1091/mbc.e10-07-0572
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发表时间：
2011-11
影响因子：
3.3
通讯作者：
Goldstein LS
中科院分区：
文献类型：
--
作者：
Henthorn KS;Roux MS;Herrera C;Goldstein LS
对运动蛋白重链（KHC）功能缺失克隆的树突和轴突表型的分析揭示了KHC在维持神经元极性以及确保适当的轴突生长方面的作用。大肠腺瘤性息肉病1被确定为KHC的相互作用伙伴，以控制神经元的定向运输和调节运动蛋白的功能。神经元的独特结构需要极性的建立和维持，这部分依赖于基于微管的运输，将必需的货物运送到树突。为了测试不同的运动蛋白差异调节模型，并了解神经元中不同的隔室如何提供必要的功能蛋白，我们以果蝇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在果蝇中被转移到适当的区域。在对树突标记人转铁蛋白受体（hTfR）错位突变体的基因筛选中，我们发现激酶重链（KHC）可能具有树突马达的功能。我们对KHC功能缺失克隆的树突和轴突表型的分析揭示了KHC在维持神经元极性以及确保适当的轴突生长方面的作用。此外，我们发现腺瘤性大肠息肉病1 （APC1）是KHC在控制定向运输和调节神经元运动蛋白功能方面的相互作用伙伴。
An analysis of dendritic and axonal phenotypes of kinesin heavy chain (KHC) loss-of-function clones revealed a role for KHC in maintaining polarity of neurons, as well as ensuring proper axonal outgrowth. Adenomatous polyposis coli 1 was identified as an interaction partner of KHC to control directed transport and modulate kinesin function in neurons. 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.