β-分泌酶与二价阳离子耐受蛋白CUTA存在相互作用  

β-secretase Interracts with Divalent Cation Tolerant Protein CUTA

作　　者：侯海波[1] 易雪莲[1] 周爱娜[1] 张云武[1] 许华曦[1] 洪水根[1] 刘润忠[1] 

机构地区：[1]厦门大学生命科学学院,生物医学研究院,分子细胞神经科学实验室,厦门361005

出　　处：《细胞生物学杂志》2008年第1期77-81,共5页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30572077);细胞生物学与肿瘤细胞工程教育部重点实验室(厦门大学)(No.2005111)资助项目~~

摘　　要：淀粉样蛋白(β-amyloid,Aβ)沉积是阿尔茨海默病(Alzheimer disease,AD)的重要病理特征之一。Aβ是由淀粉样前体蛋白(amyloid precursor protein,APP)经β-分泌酶(BACE)和γ-分泌酶水解产生的,因此BACE1在AD的形成过程中发挥重要作用。为了进一步研究BACE1的作用机制,以BACE1胞内段构建诱饵蛋白用酵母双杂交方法筛选与之相互作用的蛋白质。结果得到了二价阳离子耐受蛋白(divalent cation tolerant protein,CUTA)的阳性克隆,β-半乳糖苷酶实验表明CUTA和BACE1胞内片段存在相互作用。构建了两者全长基因的表达载体,证明二者在哺乳动物细胞中同样可以相互作用。CUTA可能涉及铜的代谢动力学及乙酰胆碱酯酶(AchE)的膜锚定,而铜的代谢失衡和AchE水平与AD发病密切相关。实验结果为BACE生物学功能和AD发病机制的研究提供了条件。The deposition of β-amyloid （Aβ） is a pathologic hallmark of Alzheimer＇s disease （AD）. Aβ is derived from β-amyloid precursor protein （APP） through sequential proteolytic cleavages by β-secretase （BACE1） and T-secretase. To further elucidate the roles of BACE1 in the development of AD, a yeast two-hybrid system was performed to screen proteins directly interacting with BACE1 from a human embryo brain cDNA library. One of the potential BACEl-interacting proteins identified from the positive clones is a copper-associated protein, divalent cation tolerant protein CUTA. The interaction between CUTA and BACE1 was confu＇med by β-galactosidase activity and co-immunoprecipitation studies. CUTA may be involved in copper dynamics and the anchoring of AchE on the plasma membrane of cells, whereas dysregulation of copper balance and AchE levels are closely correlated with AD pathogenesis, our results suggest that CUTA may plays potential roles in the regulation of BACE1 activity/function and in the pathogenesis of Alzheimer＇s disease.

关 键 词：淀粉样蛋白 阿尔茨海默病 Β-分泌酶 Γ-分泌酶 CUTA 

分 类 号：R749.1[医药卫生—神经病学与精神病学]