Morais Vanessa A, Leight Susan, Pijak Donald S, Lee Virginia M-Y, Costa Júlia
Instituto de Tecnologia Química e Biológica, Apartado 127, Oeiras 2781-901, Portugal.
FEBS Lett. 2008 Feb 6;582(3):427-33. doi: 10.1016/j.febslet.2008.01.003. Epub 2008 Jan 15.
The gamma-secretase complex, composed by presenilin, nicastrin, APH-1 and PEN-2, is involved in intramembranous proteolysis of membrane proteins, such as amyloid precursor protein or Notch. Cleavage occurs in multiple cellular compartments. Here, nicastrin mutants containing targeting signals to the endoplasmic reticulum, trans-Golgi network, lysosomes, or plasma membrane have been shown to yield active gamma-secretase complexes with different activities and specificities: wild-type and plasma membrane nicastrin complexes yielded the highest amounts of secreted amyloid-beta peptide (Abeta), predominantly Abeta40, whereas intracellular targeted mutants produced intracellular Abeta, with a comparatively higher amount of Abeta42. These results suggest that compartmental microenvironments play a role in gamma-secretase activity and specificity.
由早老素、尼卡斯特林、APH-1和PEN-2组成的γ-分泌酶复合物参与膜蛋白（如淀粉样前体蛋白或Notch）的膜内蛋白水解。切割发生在多个细胞区室中。在此，已证明含有靶向内质网、反式高尔基体网络、溶酶体或质膜的信号的尼卡斯特林突变体可产生具有不同活性和特异性的活性γ-分泌酶复合物：野生型和质膜尼卡斯特林复合物产生的分泌型淀粉样β肽（Aβ）量最高，主要是Aβ40，而细胞内靶向突变体产生细胞内Aβ，其中Aβ42的量相对较高。这些结果表明，区室微环境在γ-分泌酶活性和特异性中起作用。
