Bakowska Joanna C, Jenkins Russell, Pendleton James, Blackstone Craig
Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704, USA.
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1042-8. doi: 10.1016/j.bbrc.2005.06.201.
The hereditary spastic paraplegias comprise a group of inherited neurological disorders in which the primary manifestation is spastic weakness of the lower extremities. Troyer syndrome is an autosomal recessive form of spastic paraplegia caused by a frameshift mutation in the spartin (SPG20) gene. Currently, neither the localization nor the functions of the spartin protein are known. In this study, we generated anti-spartin antibodies and found that spartin is both cytosolic and membrane-associated. Using a yeast two-hybrid approach, we screened an adult human brain library for binding partners of spartin. We identified Eps15, a protein known to be involved in endocytosis and the control of cell proliferation. This interaction was confirmed by fusion protein "pull-down" experiments as well as a cellular redistribution assay. Our results suggest that spartin might be involved in endocytosis, vesicle trafficking, or mitogenic activity, and that impairment in one of these processes may underlie the long axonopathy in patients with Troyer syndrome.
遗传性痉挛性截瘫是一组遗传性神经疾病，其主要表现为下肢痉挛性无力。特罗耶综合征是痉挛性截瘫的一种常染色体隐性形式，由spartin（SPG20）基因的移码突变引起。目前，spartin蛋白的定位和功能均不清楚。在本研究中，我们制备了抗spartin抗体，发现spartin既存在于胞质中，也与细胞膜相关。我们采用酵母双杂交方法，在成人脑文库中筛选spartin的结合伴侣。我们鉴定出Eps15，一种已知参与胞吞作用和细胞增殖调控的蛋白。这种相互作用通过融合蛋白“下拉”实验以及细胞重分布分析得到了证实。我们的结果表明，spartin可能参与胞吞作用、囊泡运输或促有丝分裂活性，并且这些过程之一的受损可能是特罗耶综合征患者长轴突病的基础。
