Isolation of signal molecules on the secretion of amyloid precursor

阿尔茨海默病淀粉样前体蛋白（APP）由于其参与在散发性和遗传性阿尔茨海默病患者的脑中发现的淀粉样β蛋白的沉积而引起关注。人们普遍认为，APP经历了两种不同类型的加工由三种假设的蛋白酶催化。由α-分泌酶介导的一种类型涉及非淀粉样蛋白生成途径，其排除β蛋白的产生。APP的N端大片段可分泌到血清中，由于APP分子中的一些分选信号与新合成APP的命运密切相关，因此APP的细胞内分选引起了人们的极大兴趣。ER滞留信号的加入抑制APP的分泌，而ER滞留信号的缺失促进APP的分泌。这些结果表明，这些序列是重要的分泌和细胞内代谢的APP。

Alzheimer's disease amyloid precursor protein (APP) has attracted attention due to its involvement in the deposition of amyloid beta protein found in brain of both sporadic and genetic Alzheimer's disease patients. It is accepted that APP undergoes tow different types of processing catalyzed by three hypothesized proteases. One type mediated by alpha-secretase involves the non-amyloidogenic pathway, which precludes the generation of the beta protein. The N-terminal large fragment of APP is secreted into serum.The intracellular sorting of APP has attracted much interest, because some sorting signals in APP molecule are highly involved in the fate of newly-synthesized APP.We constracted two mutants, APPE19 and APPdeltaC10, which contains or deletes an endoplasmic reticulum (ER) retention signal. Addition of ER retention signal inhibied secretion of APP,while deletion of it promoted secretion. These results suggest that these sequences are important for the secretion and intracellular metabolism of APP.