Jacobsen Kristin T, Iverfeldt Kerstin
Department of Neurochemistry, Stockholm University, Stockholm, Sweden.
Cell Mol Life Sci. 2009 Jul;66(14):2299-318. doi: 10.1007/s00018-009-0020-8. Epub 2009 Mar 31.
The Alzheimer's amyloid precursor protein (APP) belongs to a conserved gene family that also includes the mammalian APLP1 and APLP2, the Drosophila APPL, and the C. elegans APL-1. The biological function of APP is still not fully clear. However, it is known that the APP family proteins have redundant and partly overlapping functions, which demonstrates the importance of studying all APP family members to gain a more complete picture. When APP was first cloned, it was speculated that it could function as a receptor. This theory has been further substantiated by studies showing that APP and its homologues bind both extracellular ligands and intracellular adaptor proteins. The APP family proteins undergo regulated intramembrane proteolysis (RIP), generating secreted and cytoplasmic fragments that have been ascribed different functions. In this review, we will discuss the APP family with focus on biological functions, binding partners, and regulated processing.
阿尔茨海默病淀粉样前体蛋白(APP)属于一个保守的基因家族,该家族还包括哺乳动物的APLP1和APLP2、果蝇的APPL以及秀丽隐杆线虫的APL-1。APP的生物学功能仍不完全清楚。然而,已知APP家族蛋白具有冗余且部分重叠的功能,这表明研究所有APP家族成员以获得更完整的认识具有重要意义。当APP首次被克隆时,有人推测它可能作为一种受体发挥作用。研究表明APP及其同源物既结合细胞外配体又结合细胞内衔接蛋白,这一理论得到了进一步证实。APP家族蛋白经历调节性膜内蛋白水解(RIP),产生具有不同功能的分泌片段和细胞质片段。在这篇综述中,我们将重点讨论APP家族的生物学功能、结合伙伴和调节加工。