Takeshita Yukio, Fujinaga Ryutaro, Kokubu Keiji, Islam Md Nabiul, Jahan Mir Rubayet, Yanai Akie, Kakizuka Akira, Shinoda Koh
Department of Neuroscience, Yamaguchi Graduate University School of Medicine, Ube, Yamaguchi, Japan.
Neuroreport. 2011 Mar 30;22(5):232-8. doi: 10.1097/WNR.0b013e32834505f4.
Huntingtin-associated protein 1 (HAP1) is an essential component of the stigmoid body (STB) and known as a possible neuroprotective interactor with causative proteins for Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia type 17 (SCA17), and Joubert syndrome. To clarify what other causative molecules HAP1/STB could interact with, we cloned normal causative genes for several neural disorders from human brain RNA library and evaluated their subcellular interaction with HAP1/STB by immunocytochemistry and immunoprecipitation after cotransfection into Neuro2a cells. The results clearly showed that HAP1/STB interacts with the normal ataxin-3 through Josephin domain and polyglutamine-expanded mutants derived from SCA3 as well. The findings suggest that HAP1/STB could modify the physiological function of normal ataxin-3 and pathogenesis of SCA3 attributable to the mutant ataxin-3.
亨廷顿蛋白相关蛋白1（HAP1）是乙状结肠小体（STB）的重要组成部分，被认为是与亨廷顿舞蹈病、脊髓延髓肌萎缩症、17型脊髓小脑共济失调（SCA17）和乔伯综合征的致病蛋白具有潜在神经保护作用的相互作用分子。为了阐明HAP1/STB还能与哪些其他致病分子相互作用，我们从人脑RNA文库中克隆了几种神经疾病的正常致病基因，并在共转染到Neuro2a细胞后，通过免疫细胞化学和免疫沉淀法评估它们与HAP1/STB的亚细胞相互作用。结果清楚地表明，HAP1/STB通过约瑟芬结构域与正常的ataxin-3以及源自SCA3的聚谷氨酰胺扩展突变体相互作用。这些发现表明，HAP1/STB可能会改变正常ataxin-3的生理功能以及由突变ataxin-3引起的SCA3的发病机制。
