PROCESSING OF THE AMYLOID PROTEIN-PRECURSOR TO POTENTIALLY AMYLOIDOGENIC DERIVATIVES
PROCESSING OF THE AMYLOID PROTEIN-PRECURSOR TO POTENTIALLY AMYLOIDOGENIC DERIVATIVES
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DOI：
10.1126/science.1738847
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发表时间：
1992-02-07
期刊：
影响因子：
56.9
通讯作者：
YOUNKIN, SG
中科院分区：
文献类型：
--
作者：
GOLDE, TE;ESTUS, S;YOUNKIN, SG
大约120千道尔顿的淀粉样β-蛋白前体（β-APP）被加工成一组复杂的8至12千道尔顿羧基末端衍生物，包括在其氨基末端或附近具有大约4千道尔顿淀粉样β-蛋白（β-AP）的潜在淀粉样形成形式。为了确定这些衍生物是否在分泌途径中或通过内体-溶酶体系统加工，（i）分析产生羧基末端衍生物和缩短的分泌衍生物的正常组的缺失突变体，和（ii）检查内体-溶酶体加工的抑制剂的作用。在分泌途径中，β-APP的裂解发生在β-AP内的单个位点，以产生一种分泌衍生物和一种非淀粉样蛋白生成羧基末端片段，而在内体-溶酶体系统中，产生一组复杂的羧基末端衍生物，包括潜在的淀粉样蛋白生成形式。
The approximately 120-kilodalton amyloid beta-protein precursor (beta-APP) is processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives that includes potentially amyloidogenic forms with the approximate 4-kilodalton amyloid beta-protein (beta-AP) at or near their amino terminus. In order to determine if these derivatives are processed in a secretory pathway or by the endosomal-lysosomal system, (i) deletion mutants that produce the normal set of carboxyl-terminal derivatives and shortened secreted derivatives were analyzed and (ii) the effect of inhibitors of endosomal-lysosomal processing was examined. In the secretory pathway, cleavage of the beta-APP occurs at a single site within the beta-AP to generate one secreted derivative and one nonamyloidogenic carboxyl-terminal fragment, whereas, in the endosomal-lysosomal system, a complex set of carboxyl-terminal derivatives is produced that includes the potentially amyloidogenic forms.