RAFT-LIKE TRANSPORT OF CYTOSKELETAL ELEMENTS IN MAMMALS

神经元的独特形态需要主动的运输机制来适当和及时地运送新合成的蛋白质，然而主动的运输给神经元带来了必须发展和维持细胞骨架轨迹以进行定向运动的负担。来自莱茵衣藻的证据表明，在鞭毛内运输(IFT)过程中，动蛋白II与大的筏状结构结合。最近克隆的NGD5，一个衣藻IFT筏子成员的同源物，增加了在哺乳动物中使用类似系统的可能性。为了测试NGD5和Kinesin II是否是哺乳动物中用于运输细胞骨架成分的类似系统的成员，有人提出了一项建议。共定位和免疫共沉淀将针对特定的神经元群体进行进一步的、更详细的分析。最终，对具有NGD5和Kinesin II目标基因中断的神经元的运输和结构的分析将被用来直接检验这一假说。有证据表明，神经丝的错误堆积可导致肌萎缩侧索硬化症(ALS)样病理。此外，轴突运输减慢是与肌萎缩侧索硬化症相关的SOD1突变毒性有关的早期事件。因此，对蛋白质转运机制的了解是我们理解神经系统的基础，并可能为神经退行性疾病的发病机制提供洞察力。

The distinct morphology of neurons requires active transport mechanisms for the appropriate and timely delivery of newly synthesized proteins, yet active transport places the burden on neurons of having to develop and maintain cytoskeletal tracks for directed locomotion. Evidence from Chlamydomonas reinhardtii indicates that kinesin II associates with large, raft-like structures during intraflagellar transport (IFT). The recent cloning of NGD5, a homologue of a member of Chlamydomonas IFT rafts, raises the possibility that an analogous system is utilized in mammals. To test if NGD5 and kinesin II are members of an analogous system in mammals utilized for transporting cytoskeletal components is proposed. Colocalization and coimmunoprecipitation will target specific neuronal population for further, more detailed analysis. Ultimately, analysis of transport and structure in neurons with targeted gene disruptions of NGD5 and kinesin II will be utilized to directly test the hypothesis. Evidence indicates that the misaccumulation of neurofilaments can lead to amyotrophic lateral sclerosis (ALS)-like pathology. Additionally, slowing of axonal transport is an early event associated with the toxicity of ALS-linked SOD 1 mutations. Therefore, an understanding of the mechanisms involved in protein transport is fundamental to our understanding of the nervous system and may provide insight into the pathogenesis of neurodegenerative diseases.