γ-分泌酶复合体对β-淀粉蛋白前体蛋白(Beta-amyloid precursor protein,βAPP)的水解是生成β-淀粉蛋白(Aβ)的关键步骤,在阿尔茨海默氏症(Alzhei mer′s disease,AD)的病理发生中起着重要作用.PEN-2蛋白(Presenilin enhancerprotein 2)是γ-分泌酶的一个重要组分,在γ-分泌酶的组装和成熟中扮演重要的角色.此外,PEN-2还具有促进神经细胞存活和防止细胞凋亡的作用.为了进一步研究PEN-2的生理功能,以PEN-2为诱饵蛋白用酵母双杂交系统筛选与之有相互作用的蛋白,发现PCBP4和GRK5肽段可结合PEN-2,并在酵母体系用β-半乳糖苷酶报告基因验证了它们的相互作用.这些结果表明PCBP4和GRK5可能影响PEN-2的正常生理功能,并且有可能在阿尔茨海默氏症的形成中起着一定的作用.Presenilin enhancer protein 2(PEN-2) is an essential component of the γ-secretase complex which plays an important role in the pathogenesis of Alzheimer′s disease(AD).In addition to PEN-2,the γ-secretase complex consists of other components including presenilin(PS),nicastrin(NCT) and Anterior pharynx defective1(APH-1).PEN-2 has been demonstrated to be crucial for the endoproteolysis of the full-length PS to generate its N-terminal fragments and C-terminal fragments,which keep associated and interact with PEN-2 and other γ-secretase components.Moreover,PEN-2 is involved in promoting neuronal cell survival and protecting neurons from apoptosis in vivo.To further understand the function of PEN-2 in the pathology of AD,we utilized PEN-2 as a bait to identify PEN-2 interacting proteins in a yeast two-hybrid system.Two candidate proteins were identified:Homo sapiens poly(rC) binding protein 4(PCBP4) and Homo sapiens G protein-coupled receptor kinase 5(GRK5).The β-galactosidase activity assay demonstrated that the two proteins can interact with PEN-2 in yeast strain AH109.These results suggest that PCBP4 and GRK5 may play potential roles in facilitating the physiological functions of PEN-2.国家自然科学基金(30572077);; 厦门市海洋与渔业局基金(k53008)资
